368 results on '"Andrew Grigg"'
Search Results
2. Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study
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Andres Forero-Torres, Tatyana Feldman, Christopher Pocock, Andrea Gallamini, John Radford, Joseph Tuscano, Yasuhiro Oki, Andrew M. Evens, Hina Jolin, Anas Younes, Keenan Fenton, Stephen M. Ansell, Joseph M. Connors, Andrew Grigg, Won Seog Kim, Ashish Gautam, Kerry J. Savage, Rachael Liu, and Monika Długosz-Danecka
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Oncology ,medicine.medical_specialty ,Neutropenia ,Dacarbazine ,Vinblastine ,Bleomycin ,chemistry.chemical_compound ,Older patients ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,polycyclic compounds ,medicine ,Humans ,Doxorubicin ,Brentuximab vedotin ,Aged ,Neoplasm Staging ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Peripheral Nervous System Diseases ,Cancer ,Hematology ,medicine.disease ,Hodgkin Disease ,ABVD ,chemistry ,business ,medicine.drug - Abstract
Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs.
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- 2021
3. Genomics analysis of leukaemia predisposition in X‐linked agammaglobulinaemia
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Andrew Grigg, Keishiro Amano, Masahiro Hirayama, Osamu Ohara, Akihiro Hoshino, Hirokazu Kanegane, Tomohiro Morio, Julian J. Bosco, Masatoshi Takagi, Takuya Naruto, Akira Nishimura, Masahiro Migita, Shotaro Iwamoto, Menno C. van Zelm, and Satoshi Miyamoto
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Genetics ,Acute megakaryoblastic leukemia ,biology ,medicine ,biology.protein ,Bruton's tyrosine kinase ,X-linked agammaglobulinemia ,Genomics ,X linked agammaglobulinaemia ,Hematology ,medicine.disease - Published
- 2021
4. Routine Blood Tests in Asymptomatic Patients With Indolent Lymphoma Have Limited Ability to Detect Clinically Significant Disease Progression
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Andrew Grigg, Zoe Loh, Joanna Chan, Geoffrey Chong, Tania Cushion, Gurjot Gill, Matthew Whybird, Eliza A Hawkes, Steven Cheema, and Oliver Piercey
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Adolescent ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Hematologic Tests ,Hematology ,Oncology (nursing) ,business.industry ,Lymphoma, Non-Hodgkin ,Health Policy ,Disease progression ,Australia ,Cancer ,Retrospective cohort study ,medicine.disease ,Lymphoma ,Indolent lymphoma ,030104 developmental biology ,Clinical research ,030220 oncology & carcinogenesis ,Disease Progression ,Neoplasm Recurrence, Local ,medicine.symptom ,business - Abstract
PURPOSE: Patients with indolent non-Hodgkin lymphoma (iNHL) undergo regular active surveillance in between treatment periods to detect disease relapse or progression. As part of surveillance, international guidelines recommend regular routine blood testing, which is based on consensus rather than evidence of utility. METHODS: We conducted a retrospective analysis of all patients older than age 16 years diagnosed with grade 1-3A follicular or marginal zone lymphoma between 2008 and 2017 from 2 Australian cancer centers to assess the utility of full blood examination, lactate dehydrogenase, and β2-microglobulin in detecting progression events, defined as either disease relapse or progression of disease. RESULTS: One hundred eighty patients attended 1,757 outpatient appointments (median follow-up, 36 months). Routine blood tests (RBTs) were performed before 83% of appointments. Seventy-four progression events occurred in 62 patients. Only 2 events (3%) were detected by RBTs alone, both of which occurred in treatment-naïve patients who subsequently developed symptoms within 3 weeks. The remainder of progression events were suspected clinically (88%) or detected by imaging (9%). RBT results were frequently abnormal in asymptomatic patients (19%), with abnormal results leading to either additional investigations or an increased surveillance frequency in 8% of cases. The overall sensitivity and positive predictive value of abnormal RBT results in detecting progression events were 39% and 9%, respectively. CONCLUSION: RBTs have poor performance characteristics and rarely detect clinically significant disease progression or relapse in asymptomatic patients with iNHL.
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- 2020
5. Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed stage III/IV Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy
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Árpád Illés, Andres Forero-Torres, Sergey Alekseev, Anas Younes, Valeria Buccheri, Keenan Fenton, Pier Luigi Zinzani, Joseph M. Connors, Anna Sureda, Andrea Gallamini, Rachael Liu, Lena Specht, Jan Walewski, Ashish Gautam, Andrew Grigg, Tae Min Kim, Graham P. Collins, Indra Purevjal, David J. Straus, Straus D., Collins G., Walewski J., Zinzani P.L., Grigg A., Sureda A., Illes A., Kim T.M., Alekseev S., Specht L., Buccheri V., Younes A., Connors J., Forero-Torres A., Fenton K., Gautam A., Purevjal I., Liu R., and Gallamini A.
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Newly diagnosed ,Vinblastine ,03 medical and health sciences ,0302 clinical medicine ,brentuximab vedotin ,primary prophylaxis ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Doxorubicin ,In patient ,Stage (cooking) ,Brentuximab vedotin ,frontline therapy ,Brentuximab Vedotin ,Chemotherapy ,business.industry ,growth factor ,Hematology ,Hodgkin Disease ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,business ,030215 immunology ,medicine.drug - Abstract
We investigate the impact of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (G-PP, N = 83) versus no G-PP (N = 579) on safety and efficacy of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) in the ECHELON-1 study of previously untreated stage III/IV classical Hodgkin lymphoma. G-PP was associated with lower incidence of ≥ grade 3 neutropenia (29% versus 70%) and febrile neutropenia (11% versus 21%). Fewer dose delays (35% versus 49%), reductions (20% versus 26%), and hospitalizations (29% versus 38%) were observed. Seven neutropenia-associated deaths occurred in the A + AVD arm; none received G-PP. A + AVD with G-PP was associated with decreased risk of a modified progression-free survival event by 26% compared with A + AVD alone (95% CI: 0.40–1.37). G-PP reduced the rate and severity of adverse events, including febrile neutropenia, reduced treatment delays, dose reductions, and discontinuations, and may thus improve efficacy outcomes. These data support G-PP for all patients treated with A + AVD.
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- 2020
6. Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience
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Loretta J. Nastoupil, Nada Hamad, John Casey, Chan Yoon Cheah, Andrew Grigg, Collin K. Chin, Peter Wood, Kate Manos, Eliza A Hawkes, Maher K. Gandhi, Katharine L Lewis, Shir Jing Ho, Bryan Do, Julie Crawford, and Samar Issa
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Lymphoma ,Central nervous system ,Disease-Free Survival ,Central Nervous System Neoplasms ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Dexamethasone ,Aged ,Aged, 80 and over ,Hematology ,business.industry ,Adenine ,Cancer ,Middle Aged ,medicine.disease ,Survival Rate ,Clinical trial ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,Female ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Primary and secondary central nervous system lymphomas (PCNSL/SCNSL) are aggressive rare malignancies with dismal outcomes. Encouraging data have emerged from Phase I/II clinical trials treating relapsed/refractory PCNSL/SCNSL with ibrutinib. We analysed 33 patients who received ibrutinib, alone or with other therapies, for PCNSL (n = 9) or SCNSL (n = 24). The objective response rate was 58% (complete response 55%). The median progression-free survival and overall survival for patients with PCNSL were both 3·1 months; for SCNSL, 10·2 and 11·5 months respectively. Only one invasive fungal infection was observed, despite concurrent or recent use of dexamethasone 8-16 mg daily in 14 patients (42%). Ibrutinib has encouraging activity in these aggressive malignancies.
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- 2020
7. Venetoclax induces rapid elimination of NPM1 mutant measurable residual disease in combination with low‐intensity chemotherapy in acute myeloid leukaemia
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Nicola E. Potter, Manohursingh Runglall, Adam Ivey, Anthony P. Schwarer, Kavita Raj, Phillip C. Nguyen, Nigel H. Russell, Chun Yew Fong, Annie‐Louise Latif, Andrew H. Wei, Tse-Chieh Teh, Andrew Grigg, Nicholas James Cummings, Ing Soo Tiong, Richard Dillon, and David Taussig
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Adult ,Male ,Oncology ,medicine.medical_specialty ,NPM1 ,Neoplasm, Residual ,Myeloid ,medicine.medical_treatment ,Azacitidine ,Short Report ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Short Reports ,AML ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Sulfonamides ,Chemotherapy ,venetoclax ,Venetoclax ,business.industry ,Nuclear Proteins ,Haematological Malignancy ‐ Clinical ,Hematology ,Middle Aged ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Neoplasm Proteins ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,MRD ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Mutation ,Cytarabine ,Female ,business ,Nucleophosmin ,030215 immunology ,medicine.drug - Abstract
Summary Based on promising results in older adults with acute myeloid leukaemia (AML), we treated patients with NPM1 mut measurable residual disease (MRD) using off‐label venetoclax in combination with low‐dose cytarabine or azacitidine. Twelve consecutive patients were retrospectively identified, including five with molecular persistence and seven with molecular relapse/progression. All patients with molecular persistence achieved durable molecular complete remission (CRMRD‐) without transplantation. Six of seven patients with molecular relapse/progression achieved CRMRD‐ after 1–2 cycles of venetoclax. This paper highlights the promising efficacy of venetoclax‐based therapy to reduce the relapse risk in patients with persistent or rising NPM1 mut MRD.
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- 2020
8. High rate of durable remissions post autologous stem cell transplantation for core-binding factor acute myeloid leukaemia in second complete remission
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Humphrey Pullon, Andrew Spencer, Julie Crawford, Andrew Grigg, Matthew J Rees, Hock Choong Lai, Frank Alvaro, Sam Milliken, Duncan Purtill, and Peter Browett
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High rate ,Transplantation ,business.industry ,Core Binding Factors ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Hematology ,Core binding factor acute myeloid leukaemia ,Transplantation, Autologous ,Leukemia, Myeloid, Acute ,Autologous stem-cell transplantation ,Cancer research ,Humans ,Medicine ,business ,Stem Cell Transplantation - Published
- 2020
9. New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation
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Ashish Bajel, Julian Lindsay, David Gottlieb, Monica A. Slavin, Michelle K Yong, Andrew Grigg, David Ritchie, Jen Kok, and William D. Rawlinson
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Ganciclovir ,medicine.medical_specialty ,T-Lymphocytes ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Hematopoietic stem cell transplantation ,030204 cardiovascular system & hematology ,Antiviral Agents ,03 medical and health sciences ,Letermovir ,0302 clinical medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,business.industry ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Maribavir ,Valganciclovir ,medicine.disease ,Transplantation ,Cytomegalovirus Infections ,business ,Viral load ,medicine.drug - Abstract
Cytomegalovirus (CMV) viraemia continues to be a frequent complication in the post-haemopoietic stem cell transplantation period despite a low incidence of CMV end-organ disease. Several significant advances in the understanding and management of CMV infection have occurred in the last few years including improved diagnostics, monitoring of CMV immunity, availability of novel anti-CMV drugs, and emerging use of immunotherapies including CMV-specific T-cell infusions. In addition to reviewing these advances we also explore some of the more practical prescribing issues of the older and newer CMV drugs including cost, toxicity and drug interactions to help clinicians navigate this new era of CMV management.
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- 2020
10. Nurse-initiated pre-prescribed antibiotic orders to facilitate prompt and appropriate antibiotic administration in febrile neutropenia
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Andrew Grigg, Jason A Trubiano, Carl M. J. Kirkpatrick, Samuel E Grigg, Karen F Urbancic, Steven T Walker, and Emma Cohen
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Male ,medicine.drug_class ,Antibiotics ,Drug Prescriptions ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Clinical pathway ,Nursing ,law ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Aged ,Febrile Neutropenia ,Retrospective Studies ,Septic shock ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Intensive care unit ,Anti-Bacterial Agents ,Hospitalization ,Intensive Care Units ,Oncology ,030220 oncology & carcinogenesis ,Administration, Intravenous ,Female ,business ,Febrile neutropenia ,Cohort study - Abstract
To assess the impact of a pathway allowing nurse initiation of first dose intravenous (IV) antibiotics on time to antibiotic administration (TTA) in adult inpatients with febrile neutropenia (FN).This study evaluated the impact on TTA of a clinical pathway (November 2017 to April 2018) allowing nurse initiation of pre-prescribed antibiotics in adult haematology patients with FN, compared with a prior cohort (November 2016 to April 2017) in which antibiotics were only prescribed and administered after medical review. The primary endpoint for comparison was TTA, calculated as the time between the first recorded fever and IV antibiotic administration. Secondary endpoints included appropriateness of initial antibiotic choice, 30-day all-cause mortality and admission to intensive care unit (ICU).Forty-seven eligible FN episodes in 40 patients and 61 episodes in 52 patients were evaluated in the pre- and post-implementation groups, respectively. Baseline characteristics were comparable between groups. Median (IQR) TTA, in the pre-implementation group [66 min (40-100 min)] was significantly prolonged versus post-implementation group [29 min (20-41 min); p 0.001]. A significantly higher proportion of episodes were administered appropriate initial antibiotics in the post-versus pre-implementation groups (100% vs. 89%, p = 0.03). There was no significant change in 30-day all-cause mortality (0% vs. 5%, p = 0.3) or ICU admission within 48 h of fever (0% vs. 2%, p 0.99) between pre- and post-implementation groups, respectively.A pathway allowing nurse initiation of pre-prescribed antibiotic orders for FN significantly reduced TTA from first recorded fever and increased the proportion of appropriate initial antibiotic choices without significantly impacting on patient outcomes.
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- 2020
11. Treatment practice and outcomes in FLT3-mutant acute myeloid leukemia in the pre-midostaurin era: a real-world experience from Australian tertiary hospitals
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Anthony P. Schwarer, Mark Droogleever, Stephen B. Ting, Chong Chyn Chua, Ing Soo Tiong, Jasmine Singh, Chun Y Fong, Lan Zhang, Andrew Grigg, Andrew H. Wei, and Andrew Lim
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Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Myeloid leukemia ,Hematology ,Intensive chemotherapy ,Clinical trial ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Oncology ,chemistry ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Treatment practice ,medicine ,Generalizability theory ,Midostaurin ,Intensive care medicine ,education ,business ,030215 immunology ,Patient factors - Abstract
Recent regulatory approval of midostaurin, a FLT3 targeting small molecular inhibitor, will likely lead to increased use of midostaurin in combination with intensive chemotherapy for patients with FLT3-mutant AML. Translation of clinical trial results into everyday practice has its challenges. This study compared the relevance of the trial population and practices studied in the midostaurin registration study (RATIFY) with real-world practice in terms of patient factors, chemotherapy, mutation-specific frequencies and clinical outcomes among patients with FLT3-mutant AML in the pre-midostaurin era (2010-2015) in Australia. We observed substantial diversity of chemotherapy regimens used in the community and limitations of the generalizability of eligibility criteria used in RATIFY (such as age and hyperleukocytosis). This study provides real-world historical data that may be used for comparison with future trial cohorts incorporating FLT3 inhibitors into the management of FLT3-mutant AML and highlights the inherent difficulties in translating clinical trial data into routine practice.
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- 2019
12. Safe administration of obinutuzumab to rituximab-intolerant patients
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Kate Manos and Andrew Grigg
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,Antibodies, Monoclonal, Humanized ,chemistry.chemical_compound ,chemistry ,Obinutuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Rituximab ,business ,Administration (government) ,medicine.drug - Published
- 2021
13. Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients : polyfunctional immune responses and lessons for clinical practice
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Lucrecia Yáñez San Segundo, Bruno Salaun, Hyeon Seok Eom, Antonio Cuneo, Ana P Gonzalez-Rodriguez, Mohamed El Idrissi, Charalambos Andreadis, Ulla Marjatta Sinisalo, Raewyn Broady, Anne Schuind, Lidia Oostvogels, Andreas Gunther, Alessandro Lucchesi, Aránzazu Alonso Alonso, Thomas C. Heineman, Alemnew F Dagnew, Isidro Jarque, Pierre Zachee, Jae Yong Kwak, Emmanuel Di Paolo, Claudia Cellini, Adriana Bastidas, Adrian Bloor, Veli-Jukka Anttila, Andrew Grigg, Thomas C. Shea, Keith M. Sullivan, Marta Polo Zarzuela, Edward A. Stadtmauer, Filiz Vural, Tampere University, Department of Internal medicine, HUS Inflammation Center, and Infektiosairauksien yksikkö
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Herpesvirus 3, Human ,Acyclovir ,law.invention ,0302 clinical medicine ,law ,Immunology and Allergy ,Herpes Zoster Vaccine ,Autologous hematopoietic stem cell transplant ,11832 Microbiology and virology ,Immunity, Cellular ,0303 health sciences ,318 Medical biotechnology ,Subunit Vaccine ,Hematopoietic Stem Cell Transplantation ,Hematopoietic stem cell ,vaccine efficacy ,3. Good health ,Virus ,Clinical Practice ,adjuvanted recombinant zoster vaccine ,cell-mediated immunity ,humoral immune response ,polyfunctionality ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Recombinant DNA ,Mediated-Immunity ,Zoster vaccine ,Stem cell ,medicine.drug ,Human ,Efficacy ,Immunology ,Vaccine Efficacy ,Herpes Zoster ,NO ,03 medical and health sciences ,Antiviral Prophylaxis ,Immune system ,Herpes-Zoster ,medicine ,Humans ,030304 developmental biology ,Pharmacology ,business.industry ,Herpesvirus 3 ,Immunity ,Vaccine efficacy ,Cellular ,3111 Biomedicine ,business - Abstract
PLAIN LANGUAGE SUMMARY What is the context? After haematopoletic stem cell transplantation, patlents have impaired immunity from conditioning chemotherapy regimens, often exacerbated by underlying diseases, putting them at high risk of developing herpes zoster. In this population, antiviral prophylaxis is the current standard of care to reduce herpes zoster risk. Vaccination provides an additional means to prevent herpes zoster. Live-attenuated vaccines are generally contraindicated in immuonocompromised patients. A non-live, adjuvanted recombinant zoster vaccine (RZV, Shingrix, GSK), has been approved for use in adults 250 years of age in the European Union, United States, Canada, Australia, Japan, and China. This vaccine is highly efficacious at preventing herpes zoster in adults over 50 years of age, as demonstrated in large, placebo-controlled randomised trials. Importantly, Shingrix use is not contraindicated in immunocompromised conditions, and was found to be highly efficacious in adults who had recently undergone autologous haematopoleticstem cell transplant. What is new? In autologous haematopoietic stem cell transplant recipients in whom Shingrix has demonstrated efficacy, two doseselicited high and persistent immune responses. Date presented here further support our understanding of the impact of specific factors such as age or underlying diseases on the vaccine's effect in the population studies, as well as the characteristics of the elicited cell-mediated immune responses. What is the impact? These results indicate that Shingrix, given shortly after haematopoletic stem cell transplant, can induce robust immune responses and reduce the risk of herpes zoster, even in individuals with immunosuppression due to underlying disease and/or use of immunosuppressive therapies, regardless of age or underlying disease. Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing >= 2 of four assessed activation markers) were similar between 18-49 and >= 50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response., GlaxoSmithKline Biologicals SA, This work was sponsored by GlaxoSmithKline Biologicals SA in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also took responsibility for all costs associated with the development and publishing of the present manuscript.
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- 2021
14. Results of a Phase 2, Randomized, Double-Blind Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)
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Michael Murray, Devendra K Hiwase, Glen A Kennedy, Nichloas Murphy, Stephen B. Ting, Ashish Bajel, Paula Marlton, Ing Soo Tiong, Harry J. Iland, Simon He, Mark J. Levis, Sam Yuen, Andrew W. Roberts, Joanna Leadbetter, Campbell Tiley, Natasha S Anstee, Meaghan Wall, Tristan Rawling, Gavin Cull, Kirk Morris, Andrew Grigg, Uyen Nguyen, Maya Latimer, Doen Ming Ong, Sundra Ravanathan, John Taper, Anthony P. Schwarer, Uwe Hahn, James D'Rozario, Ian Bilmon, Andrew H. Wei, Sun Loo, Anoop K Enjeti, and Emma Verner
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Oncology ,Sorafenib ,medicine.medical_specialty ,business.industry ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Intensive chemotherapy ,Placebo ,Biochemistry ,Double blind study ,Internal medicine ,medicine ,business ,Flt3 itd ,medicine.drug - Abstract
Introduction Midostaurin is the only approved FLT3 inhibitor for combination with intensive induction and consolidation chemotherapy in newly diagnosed patients with FLT3 mutant AML. The FLT3 inhibitor, sorafenib, was investigated in the randomized SORAML trial (Röllig, Lancet Onc 2015), in combination with intensive chemotherapy (IC) for newly diagnosed adults with AML Methods The Australasian Leukaemia and Lymphoma Group (ALLG) conducted a randomized phase 2 study [ACTRN12611001112954] in 99 adults aged 18-65 years with newly diagnosed FLT3-ITD positive (allelic ratio (AR) ≥0.05) AML to determine whether addition of SOR to IC would improve event-free survival (EFS). The study was powered to identify a 25% increase in 2-year EFS with SOR. Patients 18-55 yrs received induction with IDAC-3 (idarubicin [IDA] 12 mg/m2 D1-3 and ara-C 1.5 g/m2 BD D1,3,5,7); patients 56-65 received 7+3 (IDA 12 mg/m2 D1-3 and ara-C 100 mg/m2 D1-7 IVI). Patients were randomized 2:1 to SOR or PBO 400 mg BD on days 4-10 of induction and each consolidation cycle. Due to the pharmacokinetic interaction between SOR and azoles, antifungal prophylaxis during induction was with AmBisome 5 mg/kg IV twice weekly. For consolidation, patients 18-55 yrs received 2 cycles of IcE (IDA 9 mg/m2 D1-2, ara-C 100 mg/m2 D1-5 IVI and etoposide 75 mg/m2 D1-5), those 56-65 yrs received 2 cycles of IDAC-2 (IDA 12 mg/m2 D1-2 and ara-C 1g/m2 BD D1,3,5). Maintenance was with SOR/PBO 400 mg bd days 1-28 for 12 cycles. Allogeneic HCT (allo-HCT) was at investigator discretion. SOR/PBO was not continued post allo-HCT. The primary endpoint was EFS without censoring for allo-HCT with events defined as failure to achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi), relapse or death. Pre-specified secondary endpoints included overall response rate (ORR) defined as CR and CRi, tolerability, EFS according to FLT3-ITD AR < or ≥ 0.7 and impact of randomization on allograft outcome. Results Between Jan 2013-May 2018, 18 centers randomized 99 patients to induction with either SOR (n=65) or PBO (n=33); one patient later found to be FLT3-ITD negative was excluded. Patient characteristics are shown in Table 1. Treatment arms were balanced apart from fewer patients in the SOR arm with NPM1 mutant AML. Deliverability of therapy was comparable, with commencement of consolidation in 78% and 79% and maintenance therapy in 32% and 27% in the SOR and PBO arms, respectively. The overall response rate (ORR) was high in both arms; 91% in the SOR (CR 80%, CRi 11%) and 94% in the PBO (CR 70%, CRi 24%) arm. In the SOR arm, 5% achieved partial remission, went off study and were deemed treatment failures. With a median overall follow-up of 25 mo, there was no significant difference in EFS (HR 0.87 95% CI 0.50-1.49; P=0.61)(Fig A) or OS (HR 0.70 95% CI 0.38-1.29; P=0.26)(Fig. B), nor in a sensitivity analysis with censoring at HCT. 2 yr EFS was 47.9% (SOR) vs 45.4% (PBO) and 2-year OS 66.8% (SOR) vs 56.4% (PBO). Hematopoietic cell transplant (HCT) in CR1 was performed in 62% and 58% in the SOR and PBO arms, respectively. For patients in CR1, 2 yr OS post-HCT was 78.5% (SOR) vs 54.2% (PBO)(Fig C). Suggestive of an on-target effect against FLT3-ITD, the impact of SOR on OS appeared greater for patients with higher FLT3-ITD AR ≥0.7 (Fig. D) (Table 2). Only one early death (within 30 days) was recorded in each treatment arm. The frequency of grade 3-4 adverse events (AEs) were similar between the two arms, apart from palmar-plantar rash, reported as drug-related in 15.4% and 6.1% pts in the SOR and PBO arms, respectively. Correlative studies will be reported in a companion abstract. Conclusions SOR did not improve EFS when combined with intensive chemotherapy in adults with newly diagnosed FLT3-ITD AML. Although not powered for significance, SOR showed a trend for improved OS among patients with higher FLT3-ITD AR or receiving HCT in CR1. Further exploration of more potent FLT3 inhibitors in the pre- and post-allograft setting are warranted for patients with newly diagnosed FLT3 mutant AML. Acknowledgements: The ALLG AMLM16 trial was funded through an Australian Government NHMRC grant and a research grant from the Leukaemia Foundation of Australia. Bayer supplied sorafenib and Gilead AmBisome. Disclosures Wei: Roche: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Astra Zeneca: Honoraria, Research Funding; Janssen: Honoraria; Macrogenics: Honoraria. Enjeti:Novartis: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; Bayer: Speakers Bureau; Sanofi: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. D'Rozario:Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Marlton:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Verner:Janssen Cilag Pty Ltd.: Research Funding. Hahn:Roche: Honoraria; Astra Zeneca: Honoraria. Hiwase:Novartis Australia: Research Funding. Anstee:Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Levis:FujiFilm: Honoraria, Research Funding; Amgen: Honoraria; Daiichi-Sankyo: Honoraria; Menarini: Honoraria; Astellas: Honoraria, Research Funding. Bajel:Abbvie: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria. Roberts:Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties; Janssen: Research Funding; Servier: Research Funding; AbbVie: Research Funding. OffLabel Disclosure: Sorafenib for FLT3-ITD AML
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- 2020
15. The Impact of Sorafenib on Phospho-FLT3 Inhibition and FLT3-ITD MRD after Chemotherapy: Correlative Studies from the Phase 2 Randomized Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)
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Michael Murray, Paula Marlton, Andrew Grigg, Andrew W. Roberts, Sarah MacRaild, Tristan Rawling, James D'Rozario, Giovanna Pomilio, Adam Ivey, Anthony P. Schwarer, Glen A Kennedy, Mark J. Levis, Doen Ming Ong, Anoop K Enjeti, Ian Bilmon, Andrew H. Wei, and Natasha S Anstee
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Sorafenib ,Chemotherapy ,medicine.medical_specialty ,Venetoclax ,business.industry ,medicine.medical_treatment ,Immunology ,Myeloid leukemia ,Consolidation Chemotherapy ,Cell Biology ,Hematology ,Placebo ,Biochemistry ,law.invention ,chemistry.chemical_compound ,Maintenance therapy ,Randomized controlled trial ,chemistry ,law ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Introduction The Australasian Leukaemia and Lymphoma Group (ALLG) conducted a randomized trial (AMLM16) combining the FLT3 inhibitor sorafenib (SOR) or placebo (PBO) with intensive induction and consolidation chemotherapy, followed by 12 months of maintenance therapy in patients with FLT3-ITD mutant AML. The clinical results of the AMLM16 study are detailed in a companion abstract co-submitted to ASH 2020. We hypothesized that the optimal time to administer sorafenib would be d4-10 of induction in order to limit overlap with anthracyclines on d1-3 and to avoid high FLT3 ligand (FLT3L) levels beyond d10, which could abrogate FLT3 on-target activity and diminish the therapeutic index. Key objectives of the correlative studies were to correlate in vivo SOR activity on suppression of FLT3 phosphorylation (P-FLT3) using the plasma inhibitory assay (PIA) with relapse risk and to assess for the presence of FLT3-ITD measurable residual disease (MRD) after therapy. Methods Patients aged 18-65 years with newly diagnosed AML (excluding APML) were enrolled to a National Blood Cancer Registry; those with a FLT3-ITD mutant: wild-type allelic ratio (AR) ≥ 0.05 were eligible for enrolment to the AMLM16 study. Patients were randomized 2:1 to SOR or PBO 400mg orally bd on d4-10 of induction and each consolidation cycle in combination with intensive chemotherapy and for 12 months as maintenance monotherapy. Serum FLT3-L levels were measured by ELISA, SOR and its metabolites by mass spectrometry. SOR mediated inhibition of FLT3 was measured in serum samples using the PIA as previously described (Levis, Blood 2006) in which P-FLT3 inhibition to ≤15% baseline is defined as response. Quantitation of FLT3-ITD levels by NGS was performed at study screening and after each induction and consolidation chemotherapy cycle. Quantitation was by amplicon-based sequencing which detected ITDs >6 bp with a sensitivity of 0.001%: levels below and above this were termed measurable residual disease (MRD) negative and positive respectively. Prepared libraries were sequenced (Illumina) using 150 bp paired-end reads with a minimum coverage of 400,000 reads. Bioinformatics analysis was performed using getITD (Blätte, Leukemia, 2019). Results 98 evaluable patients were randomized to induction with either SOR (n=65) or PBO (n=33) with a FLT3-ITD AR ranging from 0.05 to 8.4. FLT3-ITD AR was ≥ 0.5 or ≥ 0.7 in 48% and 29%, respectively. During induction, FLT3-L levels increased by an average of 150-fold from d4 to d10 and a further 1.6-fold to d15, with a return to baseline by d28. Serial plasma samples to assess PIA were available for 63 patients (Fig A). Response to ≤15% on d10 (relative to d4) was observed in 88% of SOR patients, compared with 4.5% receiving PBO. The relapse risk was 32% and 62% among PIA responders and non-responders, respectively (Fig A). Among patients with PIA response to ≤15% by d10 (the last day of SOR/PBO), only 8.3% had evidence of a sustained PIA response by d15. Reduction of FLT3-ITD to undetectable levels (VAF We compared the relationship between inhibition of P-FLT3 on d10 and bone marrow FLT3-ITD MRD after induction with relapse risk (Fig D, E). In the SOR arm, if P-FLT3 was not reduced to ≤15%, all patients had persistent FLT3-ITD MRD after induction and the relapse risk was 80% (Fig D). In contrast, if P-FLT3 inhibition was ≤15% and FLT3-ITD MRD not detected, the relapse risk was only 20%. In the PBO arm after induction, persistent and undetectable FLT3-ITD MRD (VAF Conclusions These studies demonstrate that in vivo SOR inhibited P-FLT3 to ≤15% during induction in the majority of cases and was associated with reduced relapse risk. Persistent FLT3-ITD MRD post-induction was associated with a high relapse risk in both treatment arms. For patients receiving SOR, failure to reduce P-FLT3 response to ≤15% was associated with a high risk of persistent FLT3-ITD MRD and clinical relapse. Disclosures Anstee: Walter and Eliza Hall Institute: Patents & Royalties: milestone and royalty payments related to venetoclax.. Levis:Menarini: Honoraria; Amgen: Honoraria; FujiFilm: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Research Funding. Enjeti:Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Bayer: Speakers Bureau; Sanofi: Speakers Bureau. D'Rozario:Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS/ Celgene: Membership on an entity's Board of Directors or advisory committees. Marlton:AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Roberts:Janssen: Research Funding; Servier: Research Funding; AbbVie: Research Funding; Genentech: Patents & Royalties: for venetoclax to one of my employers (Walter & Eliza Hall Institute); I receive a share of these royalties. Wei:Astra Zeneca: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria, Research Funding, Speakers Bureau; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Roche: Honoraria; Macrogenics: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria. OffLabel Disclosure: Sorafenib for FLT3-ITD AML
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- 2020
16. BRENTUXIMAB VEDOTIN WITH CHEMOTHERAPY IN ADOLESCENTS AND YOUNG ADULTS (AYAS) WITH STAGE III OR IV HODGKIN LYMPHOMA: A SUBGROUP ANALYSIS FROM THE PHASE 3 ECHELON‐1 STUDY
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Ann S. LaCasce, Nancy L. Bartlett, Kerry J. Savage, David J. Straus, Harry H. Miao, Andrew Grigg, Howland E. Crosswell, Pier Luigi Zinzani, Graham P. Collins, Keenan Fenton, Cassie Dong, and Michelle A. Fanale
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Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Subgroup analysis ,Hematology ,General Medicine ,humanities ,Young age ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Hodgkin lymphoma ,Young adult ,Stage (cooking) ,business ,Brentuximab vedotin ,medicine.drug ,Rare disease - Abstract
7528 Background: Hodgkin lymphoma (HL) is a rare disease that commonly occurs in adolescents and young adults (AYAs) which is typically defined as 15 to 39 years. Given their young age at presentation, key factors in treatment selection include a high cure rate and limiting long-term toxicities. Brentuximab vedotin (Adcetris®; A) is a CD30-directed ADC approved in combination with doxorubicin, vinblastine, and dacarbazine chemotherapy (A+AVD) for adults with previously untreated stage III/IV cHL based on results from the phase 3 ECHELON-1 trial. Recent 5-year data demonstrated a significantly improved PFS per investigator (INV) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (HR, 0.69; 95% CI, 0.54–0.9; P = 0.003) (Straus 2020). Here we describe key efficacy and safety results for AYA pts enrolled in ECHELON-1. Methods: ECHELON-1 (N = 1334) is a global, open-label, multicenter, randomized trial of pts with previously untreated stage III/IV cHL. A total of 771 AYAs (57.8%) received either A+AVD (n = 396) or ABVD (n = 375) with a PET scan after cycle 2 (PET2). An analysis of PFS (time from randomization to progression or death from any cause) per INV was conducted. Results: After a median follow-up of 60.7 months (95% CI, 60.4-61.0), there was a 36% reduction in the risk of progression or death in AYAs receiving A+AVD vs ABVD (HR 0.64; 95% CI, 0.45-0.92; P = 0.013) with a 5-year PFS of 86.3% vs 79.4%, respectively, similar to the ITT population. The PFS benefit of A+AVD vs ABVD was independent of PET2 status; PET2 positivity (Deauville 4-5) was 6% and 8%, respectively. On the A+AVD arm, 81 AYAs (20%) had at least 1 subsequent anticancer therapy vs 96 AYAs (26%) on the ABVD arm; 26 AYAs (7%) received subsequent high dose chemotherapy and autologous stem cell transplant vs 32 AYAs (9%) on the A+AVD and ABVD arms, respectively. Resolution or improvement of peripheral neuropathy (PN) were similar in both arms; 224 AYAs (88%) on the A+AVD had resolution or improvement of PN vs 133 AYAs (89%) on the ABVD arm. Ongoing PN was predominantly Gr 1 (62%) and Gr 2 (26%), with 8 AYAs (13%) on the A+AVD arm and 1 AYA (5%) on the ABVD arm reporting ongoing Gr 3 PN. Finally, 7 AYAs (1.8%) and 5 AYAs (1.4%) on the A+AVD and ABVD arms, respectively, reported a secondary malignancy. Subsequent pregnancies were reported in female pts (44 A+AVD; 26 ABVD) and partners of male pts (31 A+AVD; 30 ABVD). No stillbirths were reported. All but 1 pt in each arm was < 40. Conclusions: Consistent with the ITT population, AYAs treated with A+AVD compared to ABVD had a durable PFS benefit at this significant 5-year milestone. No impact on the rate of secondary malignancies and a numerically greater number of pregnancies were observed, outcomes of interest to AYAs. Additionally, the majority of PN events improved or resolved over time. A+AVD should be considered a treatment option for AYAs with stage III/IV cHL. Clinical trial information: NCT01712490.
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- 2021
17. IMMUNE PRIMING WITH NIVOLUMAB FOLLOWED BY NIVOLUMAB & RITUXIMAB IN 1 ST LINE TREATMENT OF FOLLICULAR LYMPHOMA: THE PHASE 2 1 ST FLOR STUDY
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S. T. Lee, Rishu Agarwal, Kate Manos, David Ritchie, Colm Keane, C. Smith, Eliza A Hawkes, K. Houdyk, Allison Barraclough, Rachel Koldej, G. Chong, Andrew Grigg, T. Fancourt, Leonid Churilov, Michael Gilbertson, and J. Hawking
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Follicular lymphoma ,Priming (immunology) ,Flor ,Hematology ,General Medicine ,Immunotherapy ,medicine.disease ,Immune system ,Internal medicine ,medicine ,Indolent Non-Hodgkin Lymphoma ,Rituximab ,Nivolumab ,business ,medicine.drug - Published
- 2021
18. Nivolumab induces dynamic alterations in CD8 T-cell function and TIM-3 expression when used to treat relapsed acute myeloid leukemia after allogeneic stem cell transplantation
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Eric Wong, David Ritchie, Joanne E. Davis, Jeff Szer, Andrew Grigg, and Rachel Koldej
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Cancer Research ,Myeloid ,business.industry ,medicine.medical_treatment ,Myeloid leukemia ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Transplantation ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Cytotoxic T cell ,Stem cell ,Nivolumab ,business ,030215 immunology - Abstract
Trial registration: ClinicalTrials.gov identifier: NCT03146468.Relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (alloSCT) is a major cause of mortali...
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- 2019
19. Recommendations for the use of pegylated interferon‐α in the treatment of classical myeloproliferative neoplasms
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Andrew C. Perkins, David M. Ross, Andrew Grigg, Kate Burbury, Nathalie C. Cook, Cecily Forsyth, Wai Hoong Chan, Steven W. Lane, Forsyth, Cecily J, Chan, Wai-Hoong, Grigg, Andrew P, Cook, Nathalie C, Lane, Steven W, Burbury, Kate L, Perkins, Andrew C, and Ross, David M
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Pegylated interferon α ,Disease ,030204 cardiovascular system & hematology ,myeloproliferative neoplasms ,Polyethylene Glycols ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Pregnancy ,Pegylated interferon ,IFN treatment for MPNs ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Myelofibrosis ,Myeloproliferative neoplasm ,Myeloproliferative Disorders ,business.industry ,Australia ,Interferon-alpha ,Cancer ,medicine.disease ,Thrombosis ,pegylated IFN ,Treatment Outcome ,Hematologic Neoplasms ,Immunology ,Disease Progression ,Female ,business ,medicine.drug - Abstract
The classical myeloproliferative neoplasms (MPN) are uncommon clonal haematopoietic malignancies characterised by excessive production of mature blood cells. Clinically they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance, and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon‐α (IFN) but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side effects. The pegylated form of IFN is a long‐acting preparation which is better tolerated and its Pharmaceutical Benefits Scheme listing is likely to lead to increased usage. We review the literature on risks and benefits of IFN treatment for MPNs, suggest criteria for patient selection in each of these diseases, and discuss strategies to manage the side effects of pegylated IFN. Refereed/Peer-reviewed
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- 2019
20. Screening and Prophylaxis to Prevent Hepatitis B Reactivation
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Marion G. Peters, Joe Sasadeusz, Seng Lee Lim, Andrew Grigg, Peter Hughes, Monica A. Slavin, Geoff McColl, Joseph Doyle, James A Rickard, Kumar Visvanathan, Sue-Anne McLachlan, Peter De Cruz, Michaela Lucas, Vijaya Sundararajan, Nicholas A. Shackel, Robert G. Gish, and Alexander J. Thompson
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Oncology ,medicine.medical_specialty ,Cost effectiveness ,Hepatitis C virus ,medicine.medical_treatment ,medicine.disease_cause ,Organ transplantation ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Immunity ,Internal medicine ,Medicine ,In patient ,Mass screening ,Hepatitis B virus ,Hepatitis ,Hepatology ,business.industry ,Immunosuppression ,Immunotherapy ,Entecavir ,Hepatitis C ,Hepatitis B ,Acquired immune system ,medicine.disease ,Transplantation ,030220 oncology & carcinogenesis ,Immunology ,Rituximab ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.
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- 2019
21. Comprehensive geriatric assessment is useful in an elderly Australian population with diffuse large B‐cell lymphoma receiving rituximab‐chemotherapy combinations
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Bianca Devitt, Chan Yoon Cheah, Doen Ming Ong, Zoe Loh, Eliza A Hawkes, Geoffrey Chong, Grace Gard, Huayi Ellen Huang, Michael Ashby, Zi Y Ng, Andrew Grigg, Yee Shuen Chong, and Allison Mo
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Male ,endocrine system ,medicine.medical_specialty ,Frail Elderly ,medicine.medical_treatment ,Risk Assessment ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Activities of Daily Living ,Antineoplastic Combined Chemotherapy Protocols ,Severity of illness ,medicine ,Humans ,Prospective cohort study ,Geriatric Assessment ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,business.industry ,Hazard ratio ,Australia ,Retrospective cohort study ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy-associated toxicities. We describe the morbidity of rituximab-chemotherapy combinations among 205 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients aged ≥60 years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively-assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy-three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166 (23%) had chemotherapy delays and 26/198 (13%) ceased therapy early. CGA was associated with pre-emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three-year overall survival (OS) of CGA-fit, CGA-unfit and CGA-frail patients was 82%, 60% and 53%, respectively. Three-year progression-free survival (PFS) of CGA-fit, CGA-unfit and CGA-frail patients was 66%, 58% and 46%, respectively. OS of CGA-fit patients was not statistically different from CGA-unfit patients, but was superior to CGA-frail patients (hazard ratio 2·892, 95% confidence interval 1·275-6·559, P = 0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA-adapted treatment strategies minimize morbidity and improves survival.
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- 2019
22. Is there a role for proton pump inhibitor prophylaxis in haematology patients?
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Emma Leitinger, Lisa Hui, and Andrew Grigg
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medicine.medical_specialty ,Gastrointestinal bleeding ,medicine.drug_class ,medicine.medical_treatment ,Proton-pump inhibitor ,Inappropriate Prescribing ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outpatients ,Internal Medicine ,medicine ,Mucositis ,Humans ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Intensive care medicine ,Adverse effect ,Glucocorticoids ,Inpatients ,Chemotherapy ,Hematology ,business.industry ,Australia ,Proton Pump Inhibitors ,medicine.disease ,Hematologic Diseases ,Practice Guidelines as Topic ,Drug Therapy, Combination ,Gastrointestinal Hemorrhage ,business - Abstract
While proton pump inhibitors (PPI) are widely prescribed as prophylaxis in selected haematology inpatient and outpatients, an informal survey of haematology units around Australia found wide variations in the specific indications for their use. This is consistent with a literature review which showed a paucity of robust evidence to support their use, specifically in chemotherapy-induced mucositis, thrombocytopenia or administration of high dose glucocorticosteroids in the absence of additional risk factors. Rationalising PPI prescribing is clinically important from both a cost and safety perspective, given the emerging evidence of adverse events associated with prolonged PPI administration. A review of prescribing practices at our institution over a 14-month period found that approximately 60% of myeloma, lymphoma and autograft patients received PPI prophylaxis during and beyond chemotherapy without an accepted indication. We encourage institutions to review their PPI prescribing practices with the intent of rationalising their use, and to conduct studies aiming to fill the substantial gaps in our knowledge.
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- 2019
23. The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia
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Lucy C. Fox, Rebecca Cleary, Kate Burbury, Amy Holmes, David T Yeung, Olga Motorna, Rosemary Harrup, Kah Lok Chan, Katherine D Cummins, Anthony P. Schwarer, Jake Shortt, Andrew McQuillan, Maciek Tatarczuch, Sumita Ratnasingam, Ben Costello, Andrew Grigg, Adrian G. Minson, Shaun Fleming, Asma Ashraf, Cecily Forsyth, Wei Hsun Hsu, and Faye Putt
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Adult ,Male ,medicine.medical_specialty ,law.invention ,Safety-Based Drug Withdrawals ,Pharmacotherapy ,Randomized controlled trial ,law ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,Humans ,Vascular Diseases ,Adverse effect ,Protein Kinase Inhibitors ,Aged ,Dyslipidemias ,Retrospective Studies ,Aged, 80 and over ,Myeloid Neoplasia ,business.industry ,Incidence (epidemiology) ,Age Factors ,Australia ,Myeloid leukemia ,Imatinib ,Retrospective cohort study ,Hematology ,Middle Aged ,Pyrimidines ,Nilotinib ,Female ,business ,medicine.drug - Abstract
Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P = .022) and dyslipidemia (P = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.
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- 2019
24. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study
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Monique C. Minnema, Margaret A. Shipp, Stephen M. Ansell, Nishitha Reddy, Scott J. Rodig, Jonathon B. Cohen, Selda Samakoglu, Kazunobu Kato, Margaretha G.M. Roemer, Sarit Assouline, Philippe Armand, Anne Sumbul, Michelle Poon, Peter Johnson, Azra H. Ligon, Manish Sharma, John M. Timmerman, and Andrew Grigg
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Male ,Oncology ,Diffuse/drug therapy ,Cancer Research ,Time Factors ,Lymphoma ,Programmed Cell Death 1 Receptor ,Phases of clinical research ,Transplantation, Autologous/adverse effects ,Clinical Trial, Phase II ,Antineoplastic Agents, Immunological ,immune system diseases ,hemic and lymphatic diseases ,Immunological/adverse effects ,80 and over ,Treatment Failure ,Non-U.S. Gov't ,Aged, 80 and over ,Research Support, Non-U.S. Gov't ,Programmed Cell Death 1 Receptor/antagonists & inhibitors ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,ORIGINAL REPORTS ,Middle Aged ,Clinical Trial ,Progression-Free Survival ,Phase II ,Multicenter Study ,Nivolumab ,Lymphoma, Large B-Cell, Diffuse/drug therapy ,Disease Progression ,Female ,Lymphoma, Large B-Cell, Diffuse ,Chromosomes, Human, Pair 9 ,Human ,Pair 9 ,Antineoplastic Agents, Immunological/adverse effects ,Adult ,medicine.medical_specialty ,Autologous/adverse effects ,Antineoplastic Agents ,Research Support ,Transplantation, Autologous ,Chromosomes ,N.I.H ,Young Adult ,Research Support, N.I.H., Extramural ,Refractory ,Internal medicine ,Large B-Cell ,Journal Article ,medicine ,Humans ,Autologous transplantation ,Progression-free survival ,Hematopoietic Stem Cell Transplantation/adverse effects ,Aged ,Transplantation ,business.industry ,Extramural ,Nivolumab/adverse effects ,medicine.disease ,business ,Diffuse large B-cell lymphoma - Abstract
Purpose Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL. Methods In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1. Results Among 121 treated patients, patients in the auto-HCT–failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT–ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT–failed cohort and 6 months in the auto-HCT–ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT–failed cohort and 1.4 and 5.8 months in the auto-HCT–ineligible cohort respectively. All three patients with complete remission—3% of the auto-HCT–failed cohort—had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification. Conclusion Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
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- 2019
25. The real-world tolerability and efficacy of asparaginase in adults aged 40 years and older with Philadelphia-negative acute lymphoblastic leukemia
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Simon Wu, Christian E Bryant, Andrew Grigg, Ing Soo Tiong, Mridula Mokoonlall, Anthony P. Schwarer, Caroline Dix, James D'Rozario, and Matthew J Rees
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Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Asparaginase ,Lymphoblastic Leukemia ,Antineoplastic Agents ,chemistry.chemical_compound ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Philadelphia Chromosome ,Philadelphia negative ,Adult all ,business.industry ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Tolerability ,chemistry ,Feature (computer vision) ,Acute Disease ,business - Abstract
Pediatric-inspired acute lymphoblastic leukemia (ALL) regimens are increasingly used in adult ALL [1]. These protocols universally feature asparaginase (ASP), a bacterial enzyme which deprives ALL ...
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- 2021
26. Dilemmas in the diagnosis and pathogenesis of atypical late‐onset familial haemophagocytic lymphohistiocytosis
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Adrian Minson, Ilia Voskoboinik, and Andrew Grigg
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medicine.medical_treatment ,Immunology ,cytotoxic lymphocyte ,Case Report ,Disease ,medicine.disease_cause ,G‐CSF ,T‐cell lymphoma ,medicine ,Immunology and Allergy ,Autologous transplantation ,General Nursing ,Immunodeficiency ,natural killer cells ,business.industry ,Immunosuppression ,Combination chemotherapy ,Immune dysregulation ,RC581-607 ,medicine.disease ,Prednisolone ,Alemtuzumab ,Immunologic diseases. Allergy ,business ,medicine.drug - Abstract
Objectives A congenital loss of cytotoxic lymphocyte activity leads to a potentially fatal immune dysregulation, familial haemophagocytic lymphohistiocytosis. Until recently, this disease was uniformly associated with infants or very young children, but it appears now that the onset may be delayed for decades. As a result, some adults are being mis‐ or under‐diagnosed because of their ‘atypical’ symptoms that are not recognised as immunodeficiency. The clinical picture and histopathology can overlap with those of haematologic malignancy, further complicating the diagnostic thought process. The spectrum of atypical symptoms is poorly defined, and therefore, it is important to describe these cases and the attendant immunological and cellular changes associated with familial haemophagocytic lymphohistiocytosis, in order to improve diagnosis and prevent unintended consequences of symptomatic therapies. Methods A 45‐year‐old patient presented with suspected T‐cell lymphoma and was treated with combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone) supplemented with granulocyte‐colony stimulating factor (G‐CSF). To mobilise stem cells for autologous transplantation, the patient was then treated with high‐dose G‐CSF and rapidly developed haemophagocytic lymphohistiocytosis. Symptoms resolved temporarily with intensive immunosuppression with alemtuzumab and durably with a subsequent allograft. Results The patient was found to be a carrier of bi‐allelic mutations in the STXBP2 protein that is essential for cytotoxic lymphocyte function, and the initial diagnosis has been revised as familial haemophagocytic lymphohistiocytosis. Conclusion This case highlights the difficulty in distinguishing atypical/late‐onset familial haemophagocytic lymphohistiocytosis from a malignant process as well as a possible exacerbation of the disease with G‐CSF therapy., Familial haemophagocytic lymphohistiocytosis (FHL) is a potentially fatal disorder of immune homeostasis. While usually presenting in children, a proportion of patients develop “atypical” FHL in adolescence or adulthood. We describe a unique case of the disease in an adult patient who initially presented mimicking a T‐cell lymphoma. Our reported case highlights the difficulty in recognising and diagnosing familial HLH in patients with poorly defined suspected haematologic malignancies, as well as the possible exacerbation of the disease with commonly used cytokine therapies.
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- 2021
27. Myeloid somatic mutation panel testing in myeloproliferative neoplasms
- Author
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Andrew Grigg, Nick Viiala, Courtney Tate, Carolyn S. Grove, Wendy N. Erber, Maya Latimer, David M. Ross, Lynette C.Y. Chee, Andrew C. Perkins, Piers Blombery, Candice Thomson, Belinda B. Guo, Steven W. Lane, Kate Manos, Nada Hamad, Ashleigh P Scott, Ross, David M, Thomson, Candice, Hamad, Nada, Lane, Steven W, Manos, Kate, Grigg, Andrew P, Guo, Belinda, Erber, Wendy N, Scott, Ashleigh, Viiala, Nick, Chee, Lynette, Latimer, Maya, Tate, Courtney, Grove, Carolyn, Perkins, Andrew C, and Blombery, Piers
- Subjects
0301 basic medicine ,Polycythaemia ,Myeloid ,Somatic cell ,diagnosis ,Bioinformatics ,myeloproliferative neoplasms ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Mastocytosis, Systemic ,hemic and lymphatic diseases ,Hypereosinophilic Syndrome ,Medicine ,Humans ,Epigenetics ,Systemic mastocytosis ,Myelofibrosis ,Polycythemia Vera ,Leukemia, Neutrophilic, Chronic ,Massive parallel sequencing ,Leukemia ,Myeloproliferative Disorders ,business.industry ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,medicine.disease ,Prognosis ,mutations ,030104 developmental biology ,medicine.anatomical_structure ,PCR ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Mutation ,prognosis ,business ,Thrombocythemia, Essential - Abstract
Myeloproliferative neoplasms are characterised by somatic mutations in pathways that regulate cell proliferation, epigenetic modifications, RNA splicing or DNA repair. Assessment of the mutational profile assists diagnosis and classification, but also aids assessment of prognosis, and may guide the use of emerging targeted therapies. The most practical way to provide information on numerous genetic variants is by using massively parallel sequencing, commonly in the form of disease specific next generation sequencing (NGS) panels. This review summarises the diagnostic and prognostic value of somatic mutation testing in Philadelphia-negative myeloproliferative neoplasms: polycythaemia vera, essential thrombocythaemia, primary myelofibrosis, chronic neutrophilic leukaemia, systemic mastocytosis, and chronic eosinophilic leukaemia. NGS panel testing is increasing in routine practice and promises to improve the accuracy and efficiency of pathological diagnosis and prognosis. Refereed/Peer-reviewed
- Published
- 2021
28. Case Report: Confirmation by Metagenomic Sequencing of Visceral Leishmaniasis in an Immunosuppressed Returned Traveler
- Author
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Nicole Isles, Torsten Seemann, Eloise Williams, Jason C Kwong, Trevor J. Kilpatrick, Benjamin P Howden, Marcel Leroi, and Andrew Grigg
- Subjects
Male ,030231 tropical medicine ,03 medical and health sciences ,Immunocompromised Host ,0302 clinical medicine ,Bone Marrow ,Virology ,medicine ,Humans ,Leishmania infantum ,Travel ,biology ,business.industry ,Leishmaniasis ,Articles ,Middle Aged ,biology.organism_classification ,medicine.disease ,Leishmania ,Fingolimod ,Pancytopenia ,Infectious Diseases ,Visceral leishmaniasis ,medicine.anatomical_structure ,Italy ,Metagenomics ,Immunology ,Leishmaniasis, Visceral ,Parasitology ,Bone marrow ,business ,medicine.drug - Abstract
There has been increased interest in using metagenomic next-generation sequencing as an unbiased approach for diagnosing infectious diseases. We describe a 61-year-old man on fingolimod therapy for multiple sclerosis with an extensive travel history who presented with 7 months of fevers, night sweats, and weight loss. Peripheral blood tests showed pancytopenia and abnormal acute phase reactants. A bone marrow aspirate showed the presence of numerous intracellular and extracellular amastigotes consistent with visceral leishmaniasis (VL). Metagenomic sequencing of the bone marrow aspirate confirmed Leishmania infantum, a species widely reported in the Mediterranean region. This correlated with acquisition of VL infection during the patient's most recent epidemiological exposure in southern Italy 12 months prior. This case demonstrates the potential application of metagenomic sequencing for identification and speciation of Leishmania in cases of VL; however, further assessment is required using other more readily obtained clinical samples such as blood.
- Published
- 2020
29. Optimal oral cyclosporin dosing with concomitant posaconazole post allogeneic stem cell transplantation
- Author
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Charlotte F. M. Hughes, Andrew Grigg, and Danielle H Robinson
- Subjects
musculoskeletal diseases ,Cancer Research ,Posaconazole ,Antifungal Agents ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Dosing ,Drug toxicity ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Triazoles ,Transplantation ,Oncology ,Mycoses ,030220 oncology & carcinogenesis ,Concomitant ,Cyclosporine ,Stem cell ,business ,human activities ,030215 immunology ,medicine.drug - Abstract
Cyclosporin is an immunosuppressive agent in allogeneic hematopoietic stem cell transplantation and its metabolism is strongly affected by concomitant drugs, including posaconazole which is now extensively used as anti-fungal prophylaxis post-allograft. We undertook a retrospective audit of 29 patients undergoing their first allograft who were receiving posaconazole at the time of transition from intravenous to oral cyclosporin. This group had a median initial oral cyclosporin dose of 2.58 mg/kg bd (range 1.75-3.95) and high incidence of cyclosporin-related toxicity was noted, requiring significant dose reductions such that by day 60 the media dose was 1.60 mg/kg bd (range 0.86-3.33). We subsequently amended our dosing protocol and analyzed a further 20 patients specifying an initial oral cyclosporin dose of 2.25 mg/kg bd and found this had little impact on toxicity or requirement for dose reductions. Starting doses of no greater than 2 mg/kg bd appear optimal to prevent toxicity in allograft recipients receiving concomitant posaconazole.
- Published
- 2020
30. Follicular Lymphoma Evaluation Index (FLEX): A new clinical prognostic model that is superior to existing risk scores for predicting progression-free survival and early treatment failure after frontline immunochemotherapy
- Author
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Wolfgang Hiddemann, Carla Casulo, Federico Mattiello, Robert Marcus, Andrea Knapp, Christopher R. Bolen, Michael Herold, John F Seymour, Farheen Mir, Andrew Grigg, and Tina Nielsen
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Follicular lymphoma ,Models, Biological ,Disease-Free Survival ,law.invention ,International Prognostic Index ,Randomized controlled trial ,law ,Risk Factors ,Internal medicine ,Medicine ,FLEX ,Humans ,Progression-free survival ,Treatment Failure ,Survival rate ,Lymphoma, Follicular ,Research Articles ,Aged ,business.industry ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,humanities ,Progression-Free Survival ,Clinical trial ,Survival Rate ,Editorial‐commentaries ,Cohort ,Commentary ,Female ,Immunotherapy ,business ,Research Article ,Follow-Up Studies - Abstract
Patients with advanced‐stage follicular lymphoma (FL) who progress early after receiving first‐line therapy have poor overall survival (OS). Currently applied clinical prognostic models such as FL International Prognostic Index [FLIPI], FLIPI‐2 and PRIMA‐Prognostic Index [PRIMA‐PI] have suboptimal sensitivity and specificity to predict this poor prognosis subgroup. The primary objective was to develop a novel prognostic model, the FL Evaluation Index (FLEX) score, to identify high‐risk patients and compare its performance with FLIPI, FLIPI‐2 and PRIMA‐PI. Progression‐free survival (PFS) after first‐line immunochemotherapy was the key endpoint, while OS and progression of disease within 24 months (POD24) were also assessed. The model, which includes nine clinical variables, was developed using a cohort of patients with previously untreated advanced‐stage FL from the phase 3 GALLIUM trial ({"type":"clinical-trial","attrs":{"text":"NCT01332968","term_id":"NCT01332968"}}NCT01332968). The performance of the model was validated using data from the SABRINA trial ({"type":"clinical-trial","attrs":{"text":"NCT01200758","term_id":"NCT01200758"}}NCT01200758). In GALLIUM (n = 1004; 127 with and 877 without POD24), FLEX increased the intergroup (low‐risk/high‐risk) difference in 2‐year and 3‐year PFS rates and demonstrated superior intergroup differences in 2‐year and 3‐year OS rates compared with FLIPI, FLIPI‐2 and PRIMA‐PI. Sensitivity for a high‐risk score to predict POD24 was 60% using FLEX compared with 53% for FLIPI and FLIPI‐2, and 69% for PRIMA‐PI, while specificity was 68% for FLEX compared with 58% for FLIPI, 59% for FLIPI‐2 and 48% for PRIMA‐PI. The prognostic value of FLEX in SABRINA was similar to FLIPI. Therefore, FLEX appears to perform better than existing prognostic models in previously untreated FL, in particular for the newer treatment regimens.
- Published
- 2020
31. Urine cultures at the onset of febrile neutropenia rarely impact antibiotic management in asymptomatic adult cancer patients
- Author
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Eliza A Hawkes, Sam E Grigg, Andrew Grigg, Ortis Estacio, Patrick Date, Douglas F Johnson, and Zoe Loh
- Subjects
Adult ,Male ,Microbiological Techniques ,medicine.medical_specialty ,Adolescent ,Urinalysis ,Urinary system ,Urine ,Asymptomatic ,Tazobactam ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Chemotherapy-Induced Febrile Neutropenia ,Aged ,Febrile Neutropenia ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,Diagnostic Tests, Routine ,business.industry ,Middle Aged ,medicine.disease ,Anti-Bacterial Agents ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Female ,Gentamicin ,medicine.symptom ,business ,Febrile neutropenia ,Piperacillin ,medicine.drug - Abstract
There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital. All haematology inpatients over a 5-year period (2011–2015) were retrospectively reviewed for episodes of FN (neutrophil count 37.5 °C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed ‘asymptomatic’), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 105 colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised. Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p
- Published
- 2018
32. Prognostication of diffuse large B-cell lymphoma in the molecular era: moving beyond the IPI
- Author
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Andrew Grigg, Eliza A Hawkes, Geoffrey Chong, and Joel Wight
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cell of origin ,Disease ,Multimodal Imaging ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Chemoimmunotherapy ,Internal medicine ,Biomarkers, Tumor ,Tumor Microenvironment ,Humans ,Medicine ,Neoplasm Metastasis ,Neoplasm Staging ,Neoplasm Grading ,Hematology ,business.industry ,Prognosis ,medicine.disease ,Lymphoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Lymphoma, Large B-Cell, Diffuse ,Symptom Assessment ,business ,Diffuse large B-cell lymphoma ,Biomarkers - Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated. Adding complexity are the plethora of new clinical, biological and molecular prognostic markers described in the recent literature, most of which lack independent validation, likely act as surrogate markers for those already in common use and have yet to substantially impact on therapeutic decision making. This review comprehensively assesses the value of individual prognostic markers in the clinical setting and their potential to predict response to novel agents, and ways to optimise their use in future research.
- Published
- 2018
33. Routine blood investigations have limited utility in surveillance of aggressive lymphoma in asymptomatic patients in complete remission
- Author
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Geoffrey Chong, Zoe Loh, Andrew Grigg, Eliza A Hawkes, Ortis Estacio, Francis J. Ha, and Michael Gilbertson
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lymphoma ,Adolescent ,Aggressive lymphoma ,Context (language use) ,Sensitivity and Specificity ,Asymptomatic ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Drug Therapy ,Internal medicine ,Humans ,Medicine ,Blood test ,B-cell lymphoma ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Non-hodgkin lymphoma ,medicine.diagnostic_test ,business.industry ,Remission Induction ,Retrospective cohort study ,Combination chemotherapy ,Middle Aged ,medicine.disease ,Oncology ,Population Surveillance ,030220 oncology & carcinogenesis ,Erythrocyte sedimentation rate ,Practice Guidelines as Topic ,Female ,Neoplasm Recurrence, Local ,medicine.symptom ,business ,Hodgkin lymphoma ,030215 immunology - Abstract
Background Patients with aggressive lymphoma achieving complete remission (CR) after first-line combination chemotherapy undergo regular surveillance to detect relapse. Current international guidelines recommend routine follow-up blood tests in this context, but evidence supporting this practice is limited. Methods We conducted a multi-centre retrospective analysis of all patients diagnosed with aggressive lymphoma treated with curative-intent chemotherapy who achieved CR for at least 3 months between 2000 and 2015. An abnormal blood test was defined as any new and unexplained abnormality for full blood examination, lactate dehydrogenase or erythrocyte sedimentation rate. Results Three hundred and forty-six patients attended a total of 3084 outpatient visits; blood tests were performed at 90% of these appointments. Fifty-six (16%) patients relapsed. Routine laboratory testing detected relapse in only three patients (5% of relapses); in the remaining patients, relapse was suspected clinically (80%) or detected by imaging (15%). The sensitivity of all blood tests was 42% and the positive predictive value was 9%. No significant difference in survival was shown in patients who underwent a routine blood test within 3 months prior to relapse versus those who did not (p = 0.88). Conclusions Routine blood tests demonstrate unacceptably poor performance characteristics, have no impact on survival and thus have limited value in the detection of relapse in routine surveillance.
- Published
- 2018
34. Strategies to enhance the graft versus tumour effect after allogeneic haematopoietic stem cell transplantation
- Author
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Eric Wong, David Ritchie, Andrew Grigg, Jeff Szer, and Joanne E. Davis
- Subjects
0301 basic medicine ,T-Lymphocytes ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Secondary Prevention ,Minor histocompatibility antigen ,medicine ,Humans ,Transplantation, Homologous ,B cell ,Transplantation ,business.industry ,Graft vs Tumor Effect ,Hematopoietic Stem Cell Transplantation ,Hematology ,Killer Cells, Natural ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Immunology ,Stem cell ,business - Abstract
Relapse of haematological malignancies after allogeneic haematopoietic stem cell transplant is a major cause of mortality. The immunological mechanisms that may lead to disease relapse may include immunological immaturity prior to reconstitution of the allogeneic immune system, tumour antigen downregulation or promotion of T-cell exhaustion by interactions with the tumour microenvironment. Current therapeutic strategies for post-transplant relapse are limited in their efficacy and alternative approaches are required. In this review, we discuss the mechanisms of T and NK-cell immune evasion that facilitate relapse of haematological malignancies after allogeneic stem cell transplantation, and explore emerging strategies to augment the allogeneic immune system in order to construct a more potent graft versus tumour response.
- Published
- 2018
35. Limited utility of routine chest X-ray in initial evaluation of neutropenic fever in patients with haematological diseases undergoing chemotherapy
- Author
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Andrew Grigg, Leonid Churilov, Ortis Estacio, Amy Baker, Eliza A Hawkes, Zoe Loh, and Geoffrey Chong
- Subjects
medicine.medical_specialty ,business.industry ,Respiratory infection ,Retrospective cohort study ,Odds ratio ,Neutropenia ,medicine.disease ,Asymptomatic ,Intensive care unit ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Clinical research ,law ,030220 oncology & carcinogenesis ,Internal medicine ,Internal Medicine ,medicine ,030212 general & internal medicine ,medicine.symptom ,business ,Febrile neutropenia - Abstract
BACKGROUND: Routine chest X-ray (CXR) is recommended for neutropenic fever (NF) management however its role is relatively understudied in haematology patients. AIM: To investigate the utility of CXR in the diagnosis and management of patients with haematological conditions complicated by NF. METHODS: Retrospective, single-centre analysis of haematology patients admitted with NF between January 2011 and December 2015. Baseline demographics, treatment details and outcomes were collected from electronic patient records. CXR underwent independent radiology review. Primary endpoints were a proportion of NF episodes in which CXR detected a probable chest infection in the absence of respiratory symptoms/signs and/or resulted in a change in antibiotic management. RESULTS: Four hundred and thirty-five episodes were identified; CXR was performed in 75% of patients (65% within 2 days of NF). In 4 of 164 (2.4%) asymptomatic patients, CXR was consistent with infection, in contrast to 19 of 119 (16%) patients with clinical signs of respiratory infection. Only 3 of 283 (1.1%) CXR resulted in a change to antibiotics. CXR consistent with infection was not associated with increased mortality or increased admission length, although there was an association with intensive care unit admission (odds ratios: 7.61, 95% confidence interval: 2.04-28.31). CONCLUSION: In haematology patients with NF, CXR rarely detected chest infection or changed management in patients with no respiratory symptoms or signs. CXR in our institution is no longer part of routine assessment of NF in the absence of these features.
- Published
- 2018
36. Echocardiography has low utility in cancer patients with Staphylococcus aureus bacteraemia: findings from a retrospective study
- Author
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Geoff Chong, Ortis Estacio, Andrew Grigg, Zoe Loh, Natasha E Holmes, and Eliza A Hawkes
- Subjects
Adult ,Male ,0301 basic medicine ,Staphylococcus aureus ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Bacteremia ,Intracardiac injection ,Young Adult ,03 medical and health sciences ,Neoplasms ,Internal medicine ,medicine ,Humans ,Endocarditis ,Risk factor ,Dialysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Retrospective cohort study ,Endocarditis, Bacterial ,Middle Aged ,Staphylococcal Infections ,medicine.disease ,Oncology ,Echocardiography ,Infective endocarditis ,Female ,business ,Central venous catheter - Abstract
To describe the incidence of infective endocarditis (IE) detected on echocardiography in cancer patients with confirmed Staphylococcus aureus bacteraemia (SAB). We retrospectively identified 95 cases of SAB in cancer patients from January 2007–March 2016. Echocardiography was ordered at the discretion of the treating team, and positive findings defined according to the Modified Duke Criteria. Complicated bacteraemia was defined by prolonged bacteraemia, presence of intracardiac device/prosthetic valve, or signs of metastatic infection. Major predisposing risk factors for IE (intracardiac device, prosthetic valve, valvular disease, diabetes mellitus, renal dialysis) were present in 27% of cases. Fifty-one of 95 (54%) had a central venous catheter and 17 (18%) patients had complicated bacteraemia. Echocardiography was performed in 75/95 (79%) episodes, with transthoracic echocardiography (TTE) alone in 56, transoesophageal echocardiography (TOE) alone in 4 and both in 15. Echocardiography was diagnostic for IE in 2 patients (1 TTE, 1 TOE), including one result that led to the diagnosis of IE in a clinically unsuspected case. Four further cases of IE were diagnosed on clinical findings, resulting in an overall rate of IE of 6% (6/95). Five of these cases occurred in patients with complicated bacteraemia or ≥ 1 risk factor for IE. No patient was readmitted due to IE. IE is infrequent in cancer patients with uncomplicated SAB and no risk factors for IE. Performing echocardiography routinely in all cancer patients with SAB rarely alters diagnosis or affects antibiotic management and therefore should be reserved for patients with specific risk factors.
- Published
- 2018
37. Low dose PD-1 inhibition in relapsed refractory Hodgkin lymphoma after allogeneic stem cell transplant with concomitant active GVHD
- Author
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Andrew Grigg, Ian Bilmon, Genevieve Douglas, and Adrian G. Minson
- Subjects
0301 basic medicine ,business.industry ,medicine.medical_treatment ,Low dose ,Hematology ,Immunotherapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Text mining ,030220 oncology & carcinogenesis ,Concomitant ,Relapsed refractory ,medicine ,Cancer research ,Hodgkin lymphoma ,Stem cell ,business - Published
- 2018
38. CLINICAL OUTCOMES FROM VENETOCLAX BASED THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL LYMPHOMAS
- Author
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Andreas Kiesbye Øvlisen, Mark Hertzberg, H. Chuah, K. Bavishi, John F. Seymour, C.Y. Cheah, Constantine S. Tam, Ian Bilmon, Mark R. Dowling, David Ritchie, Henry Miles Prince, T.C. El-Galaly, Max Wolf, Robin Filshie, Nada Hamad, Katharine L Lewis, S. P'Ng, Andrew Grigg, and P. Choi
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Venetoclax ,business.industry ,Hematology ,General Medicine ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Relapsed refractory ,medicine ,In patient ,business ,B cell - Published
- 2019
39. Patient and Physician Perspectives of Unmet Needs in CML - Designing the CML SUN Survey
- Author
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Virginia Pilipovic, Nigel B. Deekes, Cristina Constantinescu, Zack Pemberton-Whiteley, Carla Boquimpani, Naoto Takahashi, Delphine Rea, Pauline Frank, Lisa Machado, Cristina Pérez Ruiz, Joannie Clements, Sung-Ho Moon, Fabian Lang, Andrew Grigg, Merula Steagall, Jorge E. Cortes, and Cornelia Borowczak
- Subjects
medicine.medical_specialty ,business.industry ,Family medicine ,Immunology ,medicine ,Cell Biology ,Hematology ,business ,Biochemistry ,Unmet needs - Abstract
Background A significant proportion (up to 37%) of patients (pts) with chronic phase (CP) CML experience either resistance or intolerance to first-line tyrosine kinase inhibitor (TKI) therapy within 5 years and transition to other treatment options(Heeg B, et al. 2021). There are limited data regarding experiences and unmet needs of pts receiving second and later TKI therapy for CML, particularly with respect to quality of life and emotional wellbeingand concerns around disease response and long-term outcome. The CML survey on unmet needs (SUN) research aims to further characterize in depth these unmet needs from the perspective of both the pts and treating physicians. Methods CML SUN consists of two sequential phases. Phase 1 entailed of 60-minute in-depth telephone qualitative interviews with adult pts on second line or later TKI treatment and physicians treating CML in France, Germany, Japan and the USA. The insights from this initial phase will inform the design of the second phase, a larger quantitative survey. This abstract reports the results of the Phase 1 qualitative research. Pts were recruited through physician referral, pt panels, pt advocacy groups and social networking service sources, while physicians treating CML were recruited via panels/databases. Key inclusion criteria can be found in Table 1. A semi-structured interview guide covering the same topics for both pts and physicians was used to conduct the interviews. The guide consisted of pre-determined but open-ended questions on the topics of perception of the disease, burden of disease, treatment journey, the impact of treatment change, adverse events (AEs), ideal treatment and needs which have not been previously identified or met. For each of the recorded interviews, a detailed content analysis was conducted to organize the collected data by themes and topics. This content analysis was used to compare responses between individuals within and across countries, and used to identify insights and trends. Results A total of 21 pts and 24 physicians were interviewed (Table 2: demographics). Physician: While physicians were mostly the ones to initiate treatment switch discussions with their pts, they typically did not provide pts with different treatment options and/or clear treatment goals when selecting 2 nd line or subsequent therapy. Most believed that pts & caregivers have minimal or no role in this matter. Therapy switch tended to happen faster if due to lack of treatment response rather than side effects which, unless severe or very frequent, were first treated symptomatically or with dose modification. Physicians felt that pts have minimal or no unmet needs requiring support when it comes to switching therapies. Patients: An almost equal proportion switched treatments due to resistance vs due to AEs. The need to switch TKI therapy induces anxiety and concerns for pts. Some pts downplayed their AEs either because of fear of triggering a therapy switch or trying to avoid being a burden. Most pts expressed the need to receive additional information on the necessity of therapy switch and on the potential therapy side effects. While physicians and pts had similar goals for the new treatment: to be effective and generally tolerable; physicians placed a higher priority to the efficacy of the treatment, whilst pts placed a higher priority to reducing the burden of AEs. Conclusions This first phase of this research has identified different perspectives and needs between CML pts and physicians in relation to change of TKI therapies, as well as potential divergencies between the two groups regarding their perception of unmet needs. This information will help design the second phase of the study which will further quantify the impact of these unmet needs in a larger population across a broad geography of 11 countries. This knowledge can be used to raise awareness and to develop support strategies to improve current CML management practices and the pt experience. Figure 1 Figure 1. Disclosures Pemberton-Whiteley: Acute Leukemia Advocates Network: Consultancy, Membership on an entity's Board of Directors or advisory committees; Leukaemia Care: Current Employment; AbbVie, Agios, Amgen, Astellas, Autolus, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Gilead, Incyte, Jazz, Janssen, Kite, Kyowa Kirin, Mallinckrodt, Novartis, Pfizer, Roche, Servier, Takeda: Consultancy, Other: Organizational grant funding, Speakers Bureau; WECAN (Workgroup of European Cancer Patient Advocacy Networks): Consultancy, Membership on an entity's Board of Directors or advisory committees; CML Advocates Network: Membership on an entity's Board of Directors or advisory committees. Cortes: Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding. Clements: Novartis Oncology: Honoraria, Other: Member of advisory board; Takeda Pharmaceuticals: Honoraria; Pfizer Pharmaceuticals: Honoraria, Other: Educational Grant; Leukemia and Lymphoma Society NPO: Membership on an entity's Board of Directors or advisory committees, Other: Patient Financial Assistance; CML Advocates Network NPO / CML Horizons Conferences: Honoraria, Membership on an entity's Board of Directors or advisory committees; The MAX Foundation NPO: Honoraria. Ruiz: Novartis: Honoraria; Pfizer: Honoraria. Rea: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Machado: Pfizer Canada: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Lang: AstraZeneca: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Takahashi: Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Research Funding; Eizai: Research Funding; Asahikasei: Research Funding; Kyowahakko-Kirin: Research Funding; Toyamakagaku: Research Funding; Ono: Research Funding. Deekes: Novartis: Honoraria. Moon: Novartis: Honoraria, Other: Member of advisory board. Grigg: Novartis: Honoraria, Other: Member of advisory board. Steagall: Novartis: Honoraria. Borowczak: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pilipovic: Novartis: Current Employment, Current equity holder in publicly-traded company. Frank: Novartis: Current Employment, Current equity holder in publicly-traded company. Constantinescu: Novartis: Other: Cristina Constantinescu is an employee of Ipsos, who were paid consultants to Novartis. Boquimpani: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pinth Pharma: Speakers Bureau.
- Published
- 2021
40. Early radiological intervention and haematology screening is associated with excellent outcomes in Budd-Chiari syndrome
- Author
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Janine French, Marcus Robertson, Andrew Grigg, Peter W Angus, Allison Mo, and Adam G Testro
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Warfarin ,Retrospective cohort study ,Liver transplantation ,medicine.disease ,Thrombosis ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Median follow-up ,030220 oncology & carcinogenesis ,Internal Medicine ,medicine ,Budd–Chiari syndrome ,030211 gastroenterology & hepatology ,business ,Transjugular intrahepatic portosystemic shunt ,Survival rate ,medicine.drug - Abstract
Background Budd–Chiari syndrome (BCS) is a rare and life-threatening disorder, resulting from thrombosis of the hepatic veins. Various treatments, including pharmacological, radiological and surgical interventions, have been used. Aim To describe retrospectively our institution's experience with management of patients with BCS. Methods A retrospective study of all cases of primary Budd–Chiari syndrome presenting to our institution between January 2000 and August 2012 was performed. Patients with secondary Budd–Chiari syndrome due to malignancy or local mass compression were excluded. Results Between 2000 and 2012, 27 patients with primary BCS presented with a median Rotterdam score of 1.16 (range: 0.07–2.11). A total of 24 patients (89%) had at least one risk factor, with the commonest being myeloproliferative neoplasm (MPN), detected in 17 of 24 (71%) of the tested patients, including four patients with normal blood counts at diagnosis. All patients were anticoagulated with warfarin or low-molecular-weight heparin (LMWH). A total of 25 (92.6%) patients also had primary radiological interventions, consisting of transjugular intrahepatic portosystemic shunt (TIPS) in 18 (67%) patients and/or angioplasty/stenting in 11 (40%). A total of 14 patients developed TIPS stenoses, requiring a median of 1.5 (range: 1–14) revisions. No patient developed TIPS failure requiring alternative therapy. Two patients were lost to follow-up. At a median follow up of 59 months (range: 2–248 months), the overall survival was 96% at 1 year and 81% at 5 years, much greater than predicted by the Rotterdam score. No patients required liver transplantation. Conclusion There is a high incidence of MPN in patients with primary BCS, including patients with normal peripheral blood counts at the time of diagnosis. Our approach of anticoagulation, aggressive and early radiological intervention aimed at rapid decompression of the congested liver resulted in excellent medium-term outcomes.
- Published
- 2017
41. Cerebral toxoplasmosis in a patient with prolonged CD4 lymphopenia post autologous hemopoietic stem cell transplant
- Author
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Andrew Grigg and Arielle van Mourik
- Subjects
CD4-Positive T-Lymphocytes ,Cancer Research ,Cyclophosphamide ,Population ,Transplantation, Autologous ,03 medical and health sciences ,0302 clinical medicine ,Lymphopenia ,parasitic diseases ,medicine ,Humans ,education ,education.field_of_study ,Leukopenia ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Brain ,Toxoplasma gondii ,Hematology ,Middle Aged ,medicine.disease ,biology.organism_classification ,Toxoplasmosis ,Lymphoma ,Transplantation ,Oncology ,Toxoplasmosis, Cerebral ,030220 oncology & carcinogenesis ,Immunology ,Female ,medicine.symptom ,Stem cell ,business ,Biomarkers ,030215 immunology ,medicine.drug - Abstract
Toxoplasma gondii is a ubiquitous protozoan parasite, which infects approximately one-third to one-half of the world’s population [1]. In the immunocompetent host, it typically causes a self-limiti...
- Published
- 2018
42. Evaluation of a Safe Neutrophil Count for Cessation of IV Antibiotics and Early Hospital Discharge in Stable, Afebrile Patients Recovering after Acute Myeloid Leukaemia (AML) Therapy or an Autograft
- Author
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Chih-Chiang Hu, Rakhee Subramanian, and Andrew Grigg
- Subjects
Chemotherapy ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Internal medicine ,Absolute neutrophil count ,Mucositis ,Cytarabine ,Medicine ,business ,Early discharge ,Busulfan ,Febrile neutropenia ,medicine.drug - Abstract
Background Currently there are no guidelines on a safe neutrophil count for intravenous antibiotic (IVAB) cessation and hospital discharge in haematology patients recovering after myelosuppressive chemotherapy complicated by febrile neutropenia (FN). Aims We assessed the safety in stable afebrile patients after recent FN of (i) appropriately stopping IVAB and (ii) early hospital discharge respectively within 24 hrs of absolute neutrophil count (ANC) recovery to ≥0.2x10^9/L. Appropriate cessation required a minimum of 3 days of IVAB and no focus of unresolved infection. Safety was defined as the absence of (i) fever recurrence after IVAB cessation and (ii) readmission in the 10-days post discharge for non-line related bacterial sepsis. Barriers to early discharge were also evaluated. Methods A retrospective, single centre audit on adult haematology patients admitted with AML (n=73 courses of induction or consolidation; 27 patients) or for an autograft (n=68 admissions;65 patients) between 2017-2019 and 2016-2017 respectively. Exclusion criteria included patients with secondary AML, reduced intensity AML chemotherapy (low dose cytarabine or azacitidine) and outpatient IVAB use post-discharge. Patients who continued on oral antibiotics as inpatients or on discharge were included in the analysis. Data were analysed with Mann Whitney U test, Chi square test and Fisher's exact test where appropriate. Results Both cohorts had a median age of 59 years. Autograft conditioning consisted mostly of high dose melphalan alone (57%) or with busulfan (7%) and BEAM (19%). All of the AML regimens contained either intermediate or high-dose cytarabine and/or an anthracycline. Most admissions (n=128; 91%) were complicated by FN, 32% (n=41) with positive blood cultures. Nearly half (n=61; 48%) of FN episodes ceased IVAB appropriately with 22/61 (36%) transitioned to oral antibiotics; another 19 (15%) episodes ceased IVAB prior to ANC ≥0.2. None of these 80 episodes had recurrent fever requiring IVAB resumption. IVAB were continued in the remaining 48 (37%) episodes, due to (a) unresolved fever (n=21) (b) recent bacteraemia or unresolved infective focus (n=17) or (c) empirically at physician discretion (n=10), for a median (range) duration of 3 (1-10), 3 (1-15) and 2 (1-5) days respectively. Thirty-seven (29%) of all FN episodes were discharged on oral antibiotics. Discharge within 24h from ANC≥0.2 occurred in 47% overall; more frequently in AML (60%) vs autograft (32%; p=0.001) patients, predominantly due to less unresolved gastrointestinal toxicity (5% vs 59% respectively). Other barriers to early discharge with an incidence of >5% included IVAB use, persistent fever, analgesia for mainly mucositis and transfusion requirement. Unplanned readmission rates were low (6% autograft, 3% AML) with none due to confirmed non-line related bacteraemia; these did not differ according to discharge ANC (≤0.5 or >0.5; p=0.217). Conclusion In afebrile, clinically stable AML and autograft patients without medico-social barriers to early discharge, IVAB can be ceased and hospital discharges safely done within 24h from recovery ANC≥0.2. Disclosures No relevant conflicts of interest to declare.
- Published
- 2020
43. Safety and Efficacy of Induction and Maintenance Avelumab Plus R-CHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Analysis of the Phase II Avr-CHOP Study
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Eliza A Hawkes, Tineke Fancourt, Joel Wight, Andrew M. Scott, Wendi Lin, Kate Manos, William Renwick, Geoffrey Chong, Joseph McKendrick, Charmaine Smith, Niles Elizabeth Nelson, Andrew Grigg, Piers Blombery, Chun Yew Fong, Allison Barraclough, Colm Keane, Sze Ting Lee, Leonid Churilov, and Joanne Hawking
- Subjects
Response rate (survey) ,Oncology ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Avelumab ,Internal medicine ,medicine ,Clinical endpoint ,Rituximab ,education ,business ,Diffuse large B-cell lymphoma ,Progressive disease ,medicine.drug - Abstract
Background: Novel strategies are needed to improve upon the 60% cure rate of upfront R-CHOP in advanced DLBCL. Single-agent immune checkpoint inhibition (ICI) has limited efficacy in heavily pre-treated DLBCL (response rate Avelumab (Av) is an anti-PDL1 monoclonal antibody with antibody dependent cell cytotoxicity (ADCC) activity which acts synergistically with rituximab (R) in vitro. We report the results of a phase II single arm study assessing safety of 1st line sequential AvR induction, R-CHOP & Av maintenance for DLBCL. Methods: Patients aged ≥18 years, ECOG 0-2 with untreated stage II-IV DLBCL and no active autoimmune disease were treated with AvR induction x2 cycles q2-weekly (Av 10mg/kg IV + R 375mg/m2 IV), followed by R-CHOP21 x 6 cycles then Av 10mg/kg x 6 cycles q2-weekly if in complete metabolic response (CMR) post R-CHOP. The primary endpoint was the rate of grade 3/4 immune-related adverse events (irAE). Secondary endpoints included overall response rate (ORR), failure free survival (FFS), overall survival (OS) and overall toxicity. Response was determined centrally by PET-CT (Lugano 2014 criteria). CMR rates by PET-CT post AvR induction and post C2 R-CHOP were exploratory endpoints. Genomic analysis was performed including next generation sequencing (NGS) based sequence variant detection, copy number analysis and structural variant detection. Results: 28 pts were enrolled from Dec 2017 to Oct 2019. Key baseline characteristics included median age 54 yrs (range 20-79); stage III/IV disease 68%; elevated LDH 61%; IPI ≥2 25%. Histology included 21 DLBCL NOS (75%; 14 GCB, 7 non-GCB by Hans algorithm), 6 primary mediastinal B-cell lymphoma (PMBCL; 21%) and 1 EBV positive DLBCL (4%). The study met its pre-specified primary endpoint of G3/4 irAE ORR post R-CHOP was 89% (all CR) (Figure 1). The ORR to 2 cycles of induction AvR was 60%, including 6 CMR (21%) across all diagnostic/histologic subgroups (n=1 PMBCL, n=2 non-GCB DLBCL, n=3 GCB DLBCL; Figures 1 and 2). Six pts (21%) progressed during AvR induction (with 1 pt completing only 1 x AvR cycle); all subsequently responded to R-CHOP. With a median follow-up of 16 months, 1-year FFS was 76% and OS 89%. Treatment was discontinued early in 5 pts; 2 during R-CHOP due to progressive disease and 3 during Av maintenance (n=1 immune hepatitis; n=1 pulmonary embolism initially reported as pneumonitis; n=1 progressive disease). Alterations in the CD274/PDCDLG2 locus were identified by NGS in 3 of 27 evaluable pts (n=2 PMBCL, n=1 EBV+ DLBCL). Full genomic analysis to identify factors associated with response will be presented. Conclusion: Sequential AvR induction, R-CHOP and Av maintenance in pts with newly diagnosed DLBCL is feasible with a manageable toxicity profile and a high CR rate. Responses to AvR alone were higher than expected based on the relapsed/refractory population and may suggest superior efficacy of ICI in the frontline setting. These results support ongoing sequential studies of immune priming with PD1/PDL1 inhibition prior to R-CHOP in DLBCL. Acknowledgements: Merck KgA for avelumab plus funding. Tour de Cure Scott Canning Early Career Grant (E Hawkes) and Wilson Centre for Lymphoma Genomics for biomarker testing. Disclosures Hawkes: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding, Speakers Bureau; BMS celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Merck Sharpe &Dohme: Membership on an entity's Board of Directors or advisory committees, Research Funding; takeda: Speakers Bureau; Merck KgA: Research Funding. Chong:Merck Serono: Research Funding; Bristol-Myers Squibb: Research Funding; Hutchison Medipharma: Research Funding; Bayer: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Servier: Research Funding; Isofol: Research Funding. Blombery:Novartis: Consultancy; Janssen: Honoraria; Amgen: Consultancy; Invivoscribe: Honoraria. Barraclough:Roche: Other: Conference sponsorship. Keane:Celgene: Honoraria, Other: Travel; BMS: Research Funding; Roche: Honoraria, Other: Travel, Speakers Bureau; MSD Oncology: Honoraria, Other: Travel; Gilead: Honoraria, Other: Travel, Speakers Bureau. Fong:Pfizer: Honoraria; Astellas: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria; AbbVie: Honoraria. Manos:Bristol-Myers Squibb: Other: Conference sponsorship. OffLabel Disclosure: Avelumab is an anti-PDL1 monoclonal antibody. Inhibition of the PD1/PDL1 pathway stimulates anti-tumour immunity.
- Published
- 2020
44. Immune priming with nivolumab followed by nivolumab and rituximab in first-line treatment of follicular lymphoma: The phase 2 1st FLOR study
- Author
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Kate Manos, Geoff Chong, Joanne Hawking, Tineke Fancourt, Colm Keane, Allison Barraclough, Kristen Houdyk, Andrew Grigg, Eliza A Hawkes, Michael Gilbertson, Rishu Agarwal, Rachel Koldej, Charmaine Smith, David Ritchie, Sze Ting Lee, and Leonid Churilov
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Follicular lymphoma ,Priming (immunology) ,medicine.disease ,First line treatment ,Immune system ,Internal medicine ,Toxicity ,Medicine ,Rituximab ,Nivolumab ,business ,Adverse effect ,medicine.drug - Abstract
7560 Background: Standard of care immunochemotherapy in front-line (1L) follicular lymphoma (FL) is highly efficacious but not without significant toxicity. High rates of grade 3-5 adverse events (AEs), primarily infection and bone marrow suppression, are experienced in up to 75% of patients. A more tolerable but equally effective approach is required. PD-1 inhibition, in combination with rituximab (R), increases T cell anti-tumour effect & enhances NK cell antibody dependent cell cytotoxicity, with proven efficacy in relapsed FL. The concept of ‘priming’ the immune system with nivolumab (N) prior to tumour-directed therapy has rationale and evidence, but the safety of this approach in 1L FL is not described. Methods: ‘1st FLOR’ (NCT03245021) is an open-label, multi-centre, phase 2, Simon’s 2-stage study of N + R (N = 39). Key eligibility were stage III-IV grade 1-3A FL requiring 1L systemic therapy; ECOG ≤2; adequate organ function. All patients (pts) receive induction N 240mg IV 2-weekly for 4 cycles. Pts with complete response (CR) receive 4 further cycles of 240mg IV N monotherapy then 12 cycles of maintenance N 480mg IV 4-weekly. Pts with < CR had 240mg N plus 375mg/m2 IV R 2-weekly for 4 cycles followed by maintenance N+R (N 480mg 4 weekly for 12 cycles; R 12 weekly for 8 cycles). Primary endpoint (EP) was ≥ G3 toxicity rate during induction. Secondary EPs; response rate by Lugano response criteria, overall toxicity, PFS, OS. Results: Between September 2017 to March 2020, 39 pts were enrolled. Baseline characteristics included median age of 54 (range: 28-79). stage IV disease in 67%, B Symptoms & bulk (≥7cm) in 23% each, intermediate-high risk FLIPI in 74%. The primary EP was met, with only 16 pts (41%) having ≥G3 toxicity at end of induction. Non-immune AEs were predominantly G1-2; most commonly infection (67%) & fatigue (64%). G3-4 Immune-related AEs were infrequent and included pancreatitis plus hepatitis (N = 1), pancreatitis alone (N = 1), rash (N = 1), transaminitis (N = 2), hypocortisolism (N = 1), hyperglycaemia (N = 3) and asymptomatic lipase/amylase increase (N = 3). Median follow-up was 17.5 months (range: 7-39). Overall response rate was 92% (36/39) with CR in 54% (21/39). Median time to CR was 5 months (m) (range: 2-25). Nine pts (23%) discontinued treatment; 7 due to progressive disease (1 pt died of transformed FL), 2 developed constitutional symptoms (1 stable disease, 1 partial response). In 25 evaluable pts, 12m PFS & OS is 72% (CI 51-88) & 96% (CI 80-100). Biomarker analysis is in progress. Conclusions: Immune-priming with single-agent N, then combination N+R in 1L FL is associated with favourable toxicity and high ORR & CR rates potentially providing an alternative to chemotherapy. Acknowledgements: Bristol-myers Squibb provided funding and nivolumab for this study. Clinical trial information: NCT03245021.
- Published
- 2021
45. Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia
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Juliana Di Iulio, Paul Cannell, Andrew W. Roberts, Anthony K. Mills, Warwick J. Benson, Andrew H. Wei, James D'Rozario, John Moore, Mark P. Hertzberg, Emma Link, Ray M. Lowenthal, Michael F. Leahy, Luke Coyle, Campbell Tiley, John Taper, Phillip Campbell, Lynda J. Campbell, Ian D. Lewis, Ilona Cunningham, A Enno, Philip A. Rowlings, Peter G Bardy, Jeff Szer, Paula Marlton, Andrew Grigg, Anthony P. Schwarer, Uwe Hahn, Kenneth F. Bradstock, Kimberly Cartwright, Devinder Gill, John F. Seymour, Gavin Cull, and Sandra Deveridge
- Subjects
Adult ,Male ,0301 basic medicine ,Acute promyelocytic leukemia ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Gene mutation ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Idarubicin ,Survival rate ,Etoposide ,Dose-Response Relationship, Drug ,business.industry ,Cumulative dose ,Cytarabine ,Adult Acute Myeloid Leukemia ,Consolidation Chemotherapy ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Nucleophosmin ,medicine.drug - Abstract
Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m2 daily for 5 days, etoposide 75 mg/m2 daily for 5 days, and idarubicin 9 mg/m2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3–internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3–internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.
- Published
- 2017
46. The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia
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Rebecca Cleary, Sumita Ratnasingam, Amy Holmes, David T Yeung, Rosemary Harrup, Shaun Fleming, Jake Shortt, Asma Ashraf, Cecily Forsyth, Maciek Tatarczuch, Kate Burbury, Ben Costello, Andrew Grigg, Wei-Hsun Hsu, Lucy C Fox, Katherine D Cummins, Olga Motorna, Andrew McQuillan, Faye Putt, Anthony P. Schwarer, and Kah-Lok Chan
- Subjects
medicine.medical_specialty ,Myeloid Neoplasia ,business.industry ,Pleural effusion ,Myeloid leukemia ,Imatinib ,Hematology ,medicine.disease ,Effective dose (pharmacology) ,Gastroenterology ,Dasatinib ,03 medical and health sciences ,0302 clinical medicine ,Effusion ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,Adverse effect ,030215 immunology ,medicine.drug ,Chronic myelogenous leukemia - Abstract
Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.
- Published
- 2017
47. Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab)
- Author
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Rodney Smith, Tae Min Kim, S. Osborne, Franco Aversa, E. Capochiani, Wolfram Brugger, Caterina Plenteda, F. Re, Andrew Grigg, Peter Trask, and Mathias J. Rummel
- Subjects
Adult ,Male ,Oncology ,Bendamustine ,medicine.medical_specialty ,Vincristine ,Population ,Follicular lymphoma ,Antineoplastic Agents ,Pharmacology ,CHOP ,Infusions, Subcutaneous ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Prednisone ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Infusions, Intravenous ,education ,Lymphoma, Follicular ,Aged ,education.field_of_study ,Cross-Over Studies ,business.industry ,Patient Preference ,Hematology ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Background The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients and methods Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6–8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. Results At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Conclusion Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. Registered clinical trial number NCT01724021 (ClinicalTrials.gov).
- Published
- 2017
48. Safety and efficacy of obinutuzumab with CHOP or bendamustine in previously untreated follicular lymphoma
- Author
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Marcos González Díaz, Andrew Grigg, Simon Rule, Martin J. S. Dyer, Martin Dreyling, Paula Marlton, Elisabeth Wassner-Fritsch, Guiyuan Lei, and Andrea Knapp
- Subjects
Adult ,Male ,Oncology ,Bendamustine ,Vincristine ,medicine.medical_specialty ,Non-Hodgkin Lymphoma ,Follicular lymphoma ,CHOP ,Antibodies, Monoclonal, Humanized ,Maintenance Chemotherapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Maintenance therapy ,Obinutuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Bendamustine Hydrochloride ,Humans ,030212 general & internal medicine ,Neoplasm Metastasis ,Cyclophosphamide ,Lymphoma, Follicular ,Survival rate ,Aged ,Neoplasm Staging ,business.industry ,Induction chemotherapy ,Induction Chemotherapy ,Articles ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Tumor Burden ,Surgery ,Treatment Outcome ,chemistry ,Doxorubicin ,030220 oncology & carcinogenesis ,Prednisone ,Female ,Drug Monitoring ,business ,Follow-Up Studies ,medicine.drug - Abstract
The GAUDI study assessed safety and preliminary efficacy of induction therapy with obinutuzumab plus chemotherapy, followed by maintenance therapy with obinutuzumab alone, in previously untreated patients with follicular lymphoma. Assignment to chemotherapy was decided on a per-center basis before the patients’ enrollment. Patients (n=81) received four to six cycles of obinutuzumab plus bendamustine every 4 weeks or six to eight cycles of obinutuzumab plus CHOP every 3 weeks. Patients with an end-of-treatment response were eligible for obinutuzumab maintenance therapy every 3 months for 2 years or until disease progression. Induction treatment was completed by 90% of patients in the obinutuzumab plus bendamustine group and 95% in the obinutuzumab plus CHOP group, while maintenance was completed by 81% and 72% of patients, respectively. All patients experienced at least one adverse event during induction, most commonly infusion-related reactions (58%), the majority of which were grade 1/2. The most common hematologic adverse event was grade 3/4 neutropenia (36% during induction and 7% during maintenance). One treatment-related death occurred during the maintenance phase. At the end of induction, 94% of patients had achieved an overall response, with complete response based on computed tomography in 36%. The progression-free survival rate at 36 months was 90% in the obinutuzumab plus bendamustine group and 84% in the obinutuzumab plus CHOP group. These results demonstrate that induction therapy with obinutuzumab plus bendamustine or obinutuzumab plus CHOP, followed by obinutuzumab maintenance, is associated with tolerable safety and promising efficacy. This study is registered at ClinicalTrials.gov as NCT00825149.
- Published
- 2016
49. Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14
- Author
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Judith Trotman, Gavin Cull, Amanda Johnston, Mark Hertzberg, Ian D. Lewis, Shir-Jing Ho, Pauline Warburton, Andrew Wirth, Devinder Gill, John Taper, Anne-Marie Watson, Sam Milliken, Michael S Hofman, Keith Fay, Rodney J. Hicks, Belinda Butcher, John F Seymour, Andrew Grigg, Maher K. Gandhi, Uwe Hahn, Robin Filshie, Geoff Chong, George Kannourakis, and William Renwick
- Subjects
Male ,0301 basic medicine ,Melphalan ,Oncology ,Aggressive lymphoma ,Carboplatin ,Antibodies, Monoclonal, Murine-Derived ,0302 clinical medicine ,International Prognostic Index ,Antineoplastic Combined Chemotherapy Protocols ,Etoposide ,Podophyllotoxin ,Cytarabine ,Antibodies, Monoclonal ,Articles ,Hematology ,Middle Aged ,Treatment Outcome ,Vincristine ,030220 oncology & carcinogenesis ,Retreatment ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Young Adult ,03 medical and health sciences ,Fluorodeoxyglucose F18 ,Median follow-up ,Internal medicine ,medicine ,Humans ,Ifosfamide ,Cyclophosphamide ,Aged ,business.industry ,medicine.disease ,Carmustine ,Transplantation ,030104 developmental biology ,Doxorubicin ,Positron-Emission Tomography ,Prednisone ,business ,Nuclear medicine ,Diffuse large B-cell lymphoma - Abstract
In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).
- Published
- 2016
50. Use of computed tomography abdomen and pelvis for investigation of febrile neutropenia in adult haematology patients
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Andrew Grigg, Hui Yin Lim, Michael Ashby, and Bronwyn Williams
- Subjects
medicine.medical_specialty ,Hematology ,medicine.diagnostic_test ,business.industry ,medicine.drug_class ,Antibiotics ,Computed tomography ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Internal Medicine ,Medicine ,Abdomen ,030212 general & internal medicine ,Radiology ,Myeloid leukaemia ,business ,Pelvis ,Febrile neutropenia - Abstract
We retrospectively evaluated the use of computed tomography abdomen and pelvis (CTAP) in febrile neutropenic autologous stem cell transplant (ASCT) and acute myeloid leukaemia (AML) patients. CTAP was more common in ASCT patients (59%) compared with AML (31%; P
- Published
- 2016
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