82 results on '"Juan Pablo Alderuccio"'
Search Results
2. Predictive value of staging PET/CT to detect bone marrow involvement and early outcomes in marginal zone lymphoma
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Juan Pablo Alderuccio, Isildinha M. Reis, Jean L. Koff, Melissa C. Larson, Dai Chihara, Wei Zhao, Sara Haddadi, Thomas M. Habermann, Peter Martin, Jennifer R. Chapman, Christopher Strouse, Brad S. Kahl, Jonathon B. Cohen, Jonathan W. Friedberg, James R. Cerhan, Christopher R. Flowers, and Izidore S. Lossos
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2023
3. Outcomes of patients with <scp>limited‐stage</scp> plasmablastic lymphoma: A <scp>multi‐institutional</scp> retrospective study
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Brian T. Hess, Anshu Giri, Yeonhee Park, Krina K. Patel, Brian K. Link, Grzegorz S. Nowakowski, Seth M. Maliske, Sonia Fortin, Julio C. Chavez, Hayder Saeed, Brian T. Hill, Alex V. Mejia Garcia, Kami J. Maddocks, Walter Hanel, Nina D. Wagner‐Johnston, Marcus R. Messmer, Brad S. Kahl, Marcus Watkins, Juan Pablo Alderuccio, Izidore S. Lossos, Sunita Nathan, Victor M. Orellana‐Noia, Craig A. Portell, Daniel J. Landsburg, Emily C. Ayers, and Jorge J. Castillo
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Hematology - Abstract
Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1-196), the 3-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3-year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper-CVAD or auto-SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.
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- 2023
4. Extranodal Marginal Zone Lymphomas Show Recurrent Mutations in DNA Repair Genes, Cancer-Associated Proliferative Signaling and NOTCH1 Signaling Pathways, Regardless of Anatomic Site
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Jennifer R Chapman-Fredricks, Devang Thakkar, Juan Pablo Alderuccio, Kikkeri N Naresh, Sarah L. Ondrejka, Eric D. Hsi, Mina L Xu, Nathan Paulson, Jean L. Koff, David L Jaye, Jonathon B. Cohen, Anne Ortved Gang, Rebecca J Leeman-Neill, Tushar Dave, Lanie Happ, Cassandra Love, Sasan Zandi, Hina Naushad, Emily F Mason, Abner Louissaint, Haley Martin, Choon Kiat Ong, Raju Pillai, Mette Ø Pedersen, C. Cameron Yin, William Choi, Rex Kwok Him Au-Yeung, Marja-Liisa Karjalainen-Lindsberg, Amy Chadburn, Vincent Sarno, Matthew McKinney, Payal Sojitra, Andrew G Evans, Amir Behdad, Carlos Galvez, Chee Leong Cheng, Magdalena Czader, Jiong Yan, Sandeep S. Dave, and Izidore S. Lossos
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Metabolic Tumor Volume Predicts Outcomes in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated with Loncastuximab Tesirine in the Lotis-2 Trial
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Juan Pablo Alderuccio, Russ A Kuker, Isildinha M Reis, Muthiah Nachiappan, Brad S. Kahl, Mehdi Hamadani, Weiyun Z. Ai, John Radford, Melhem Solh, Kirit M. Ardeshna, Brian T. Hess, Matthew A. Lunning, Pier Luigi Zinzani, Anastasios Stathis, Carmelo Carlo-Stella, Eric Yu, Paolo F Caimi, Deukwoo Kwon, Izidore S. Lossos, Fei Yang, and Craig H. Moskowitz
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Long‐term outcomes of patients with conjunctival extranodal marginal zone lymphoma
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Eduardo Edelman Saul, Juan Pablo Alderuccio, Isildinha M. Reis, Wei Zhao, Sunil G. Iyer, Gregor Rodriguez, Amrita Desai, Jennifer R. Chapman, David T. Tse, Arnold M. Markoe, Derek M. Isrow, and Izidore S. Lossos
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Hematology - Abstract
Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%-79.8%) and 89.4% (95% CI 77.4%-95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%-35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1-2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age 60 years (PFS: HR = 2.93, 95% CI 1.08-7.95; p = .035, OS: HR = 9.07, 95% CI 1.17-70.26; p = .035) and MALT-IPI 1-2 (PFS: HR = 2.67, 95% CI 1.12-6.31; p = .027, OS: HR = 6.64, 95% CI 1.45-30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04-0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12-0.96 p = .041 and SHR = 0.11, 95% CI 0.03-0.36; p .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure.
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- 2022
7. A Deep Learning-Aided Automated Method for Calculating Metabolic Tumor Volume in Diffuse Large B-Cell Lymphoma
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Russ A. Kuker, David Lehmkuhl, Deukwoo Kwon, Weizhao Zhao, Izidore S. Lossos, Craig H. Moskowitz, Juan Pablo Alderuccio, and Fei Yang
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Cancer Research ,Oncology ,artificial intelligence ,deep learning ,U-Net ,PET/CT ,diffuse large B-cell lymphoma ,metabolic tumor volume - Abstract
Metabolic tumor volume (MTV) is a robust prognostic biomarker in diffuse large B-cell lymphoma (DLBCL). The available semiautomatic software for calculating MTV requires manual input limiting its routine application in clinical research. Our objective was to develop a fully automated method (AM) for calculating MTV and to validate the method by comparing its results with those from two nuclear medicine (NM) readers. The automated method designed for this study employed a deep convolutional neural network to segment normal physiologic structures from the computed tomography (CT) scans that demonstrate intense avidity on positron emission tomography (PET) scans. The study cohort consisted of 100 patients with newly diagnosed DLBCL who were randomly selected from the Alliance/CALGB 50,303 (NCT00118209) trial. We observed high concordance in MTV calculations between the AM and readers with Pearson's correlation coefficients and interclass correlations comparing reader 1 to AM of 0.9814 (ip/iamp;lt; 0.0001) and 0.98 (ip/iamp;lt; 0.001; 95%CI = 0.96 to 0.99), respectively; and comparing reader 2 to AM of 0.9818 (ip/iamp;lt; 0.0001) and 0.98 (ip/iamp;lt; 0.0001; 95%CI = 0.96 to 0.99), respectively. The Bland-Altman plots showed only relatively small systematic errors between the proposed method and readers for both MTV and maximum standardized uptake value (SUVmax). This approach may possess the potential to integrate PET-based biomarkers in clinical trials.
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- 2022
8. Revised MALT-IPI: A new predictive model that identifies high-risk patients with extranodal marginal zone lymphoma
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Juan Pablo Alderuccio, Isildinha M. Reis, Thomas M. Habermann, Brian K. Link, Catherine Thieblemont, Annarita Conconi, Melissa C. Larson, Luciano Cascione, Wei Zhao, James R. Cerhan, Emanuele Zucca, and Izidore S. Lossos
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Risk Factors ,Humans ,Hematology ,Lymphoma, B-Cell, Marginal Zone ,Middle Aged ,Prognosis ,Retrospective Studies - Abstract
Extranodal marginal zone lymphoma (EMZL) is a heterogeneous disease with a subset of patients exhibiting a more aggressive course. We previously reported that EMZL with multiple mucosal sites (MMS) at diagnosis is characterized by shorter survival. To better recognize patients with different patterns of progression-free survival (PFS) we developed and validated a new prognostic index primarily based on patient's disease characteristics. We derived the "Revised mucosa-associated lymphoid tissue International Prognostic Index" (Revised MALT-IPI) in a large data set (n = 397) by identifying candidate variables that showed highest prognostic association with PFS. The revised MALT-IPI was validated in two independent cohorts, from the University of Iowa/Mayo Clinic (n = 297) and from IELSG-19 study (n = 400). A stepwise Cox regression analysis yielded a model including four independent predictors of shorter PFS. Revised MALT-IPI has scores ranging from 0 to 5, calculated as a sum of one point for each of the following- age60 years, elevated LDH, and stage III-IV; and two points for MMS. In the training cohort, the Revised MALT-IPI defined four risk groups: low risk (score 0, reference group), low-medium risk (score 1, HR = 1.85, p = .008), medium-high risk (score 2, HR = 3.84, p .0001), and high risk (score 3+, HR = 8.48, p .0001). Performance of the Revised MALT-IPI was similar in external validation cohorts. Revised MALT-IPI is a new index centered on disease characteristics that provides robust risk-stratification identifying a group of patients characterized by earlier progression of disease. Revised MALT-IPI can allow a more disease-adjusted management of patients with EMZL in clinical trials and practice.
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- 2022
9. Diffuse large B-cell lymphoma of the Waldeyer's ring: A U.S. population-based survival analysis
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Jorge A. Florindez, Izidore S. Lossos, and Juan Pablo Alderuccio
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Cancer Research ,Oncology ,Hematology ,General Medicine - Published
- 2022
10. A roadmap for clinical trial design in marginal zone lymphoma
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Juan Pablo Alderuccio, Thomas Habermann, Russ Kuker, Craig H. Moskowitz, Andrew D. Zelenetz, and Izidore S. Lossos
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Clinical Trials as Topic ,Humans ,Hematology ,Lymphoma, B-Cell, Marginal Zone - Abstract
Marginal zone lymphoma (MZL) is commonly underrepresented in clinical trials collectively studying mostly nodal indolent lymphomas.In this manuscript we propose new inclusion and response criteria defined by MZL subtype and disease location for those with extranodal MZL. Progression of disease within 24 months is associated with poor outcomes in MZL and future studies should assess the efficacy of novel agents in this population.
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- 2022
11. EBV‐positive HIV‐associated diffuse large B cell lymphomas are characterized by JAK/STAT (STAT3) pathway mutations and unique clinicopathologic features
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Joo Y. Song, Alyssa Bouska, Jennifer R. Chapman, Lisa M. Rimsza, Shuhua Yi, Francisco Vega, Alanna Maguire, Izidore S. Lossos, Wing C. Chan, Juan Pablo Alderuccio, and Weiwei Zhang
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Adult ,Male ,STAT3 Transcription Factor ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.medical_specialty ,Cell of origin ,HIV Infections ,Context (language use) ,medicine.disease_cause ,Gastroenterology ,Virus ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,EP300 ,B cell ,Janus Kinases ,Mutation ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,BCL6 ,Lymphoma ,STAT Transcription Factors ,medicine.anatomical_structure ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Signal Transduction - Abstract
Even in the era of highly active combination antiretroviral therapy (cART), patients with HIV have a disproportionate risk of developing aggressive lymphomas that are frequently Epstein-Barr virus (EBV)-related. Here, we investigate HIV-associated diffuse large B-cell lymphoma (HIV-DLBCL) and compare EBV-positive and EBV-negative cases. HIV-DLBCL were identified from two academic medical centres and characterised by immunohistochemistry, EBV status, fluorescence in situ hybridisation, cell of origin determination by gene expression profiling, and targeted deep sequencing using a custom mutation panel of 334 genes. We also applied the Lymphgen tool to determine the genetic subtype of each case. Thirty HIV-DLBCL were identified, with a median patient age of 46 years and male predominance (5:1). Thirteen cases (48%) were EBV-positive and 14 (52%) EBV-negative. Nine of the 16 tested cases (56%) had MYC rearrangement, three (19%) had BCL6 (two of which were double hit MYC/BCL6) and none had BCL2 rearrangements. Using the Lymphgen tool, half of the cases (15) were classified as other. All HIV-DLBCL showed mutational abnormalities, the most frequent being TP53 (37%), MYC (30%), STAT3 (27%), HIST1H1E (23%), EP300 (20%), TET2 (20%), SOCS1 (17%) and SGK1 (17%). EBV-negative cases were mostly of germinal centre B-cell (GCB) origin (62%), showed more frequent mutations per case (a median of 13·5/case) and significant enrichment of TP53 (57% vs. 15%; P = 0·046), SGK1 (36% vs. 0%; P = 0·04), EP300 (43% vs. 0%; P = 0·02) and histone-modifying gene (e.g. HIST1H1E, HIST1H1D, 79% vs. 31%; P = 0·02) mutations. EBV-positive cases were mostly of non-GCB origin (70%), with fewer mutations per case (median 8/case; P = 0·007), and these tumours were enriched for STAT3 mutations (P = 0·10). EBV-positive cases had a higher frequency of MYC mutations but the difference was not significant (36% vs. 15%; P = 0·38). EBV-association was more frequent in HIV-DLBCLs, arising in patients with lower CD4 counts at diagnosis (median 46·5 vs. 101, P = 0·018). In the era of cART, approximately half of HIV-DLBCL are EBV-related. HIV-DLBCL are enriched for MYC rearrangements, MYC mutations and generally lack BCL2 rearrangements, regardless of EBV status. Among HIV-DLBCL, tumours that are EBV-negative and EBV-positive appear to have important differences, the latter arising in context of lower CD4 count, showing frequent non-GCB origin, lower mutation burden and recurrent STAT3 mutations.
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- 2021
12. Primary thyroid lymphoma: survival analysis of SEER database (1995–2016)
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Isildinha M. Reis, Izidore S. Lossos, Juan Pablo Alderuccio, and Jorge A. Florindez
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Oncology ,endocrine system ,Cancer Research ,medicine.medical_specialty ,Lymphoma ,endocrine system diseases ,Seer database ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Thyroid lymphoma ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Thyroid Neoplasms ,Survival analysis ,business.industry ,Thyroid ,Hematology ,medicine.disease ,Survival Analysis ,Survival Rate ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,embryonic structures ,Lymph ,business ,SEER Program ,030215 immunology - Abstract
Primary thyroid lymphoma (PTL) is an uncommon type of non-Hodgkin lymphoma (NHL) affecting thyroid gland only. Some investigators also consider patients with adjacent lymph nodes as PTL [1]. It acc...
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- 2021
13. Calculation of Metabolic Tumor Volume in Diffuse Large B-Cell Lymphoma Using a Deep Learning-Aided Automated Method
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Juan Pablo Alderuccio, Russ A. Kuker, David Lehmkuhl, Deukwoo Kwon, Andrea Cordoba, Weizhao Zhao, Izidore S. Lossos, Craig H. Moskowitz, and Fei Yang
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
14. Predictive Value of Staging PET/CT to Detect Bone Marrow Involvement in Marginal Zone Lymphoma (MZL): An Analysis from LEO MZL Working Group
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Juan Pablo Alderuccio, Isildinha M Reis, Jean L. Koff, Melissa C. Larson, Dai Chihara, Wei Zhao, Sara Haddadi, Thomas M. Habermann, Peter Martin, Jennifer R Chapman-Fredricks, Christopher Strouse, Brad S. Kahl, Jonathon B. Cohen, Jonathan W. Friedberg, James R. Cerhan, Christopher R. Flowers, and Izidore S. Lossos
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
15. Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study
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Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K. Moyo, Nishitha Reddy, Julia Sheets, David M. Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C. Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F. Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A. David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P. Kenkre, Adam J. Olszewski, Jonathon B. Cohen, Neil Palmisiano, Elvira Umyarova, Ryan A. Wilcox, Farrukh T. Awan, Juan Pablo Alderuccio, Stefan K. Barta, Natalie S. Grover, Nilanjan Ghosh, Nancy L. Bartlett, Alex F. Herrera, and Geoffrey Shouse
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Cancer Research ,Clinical Trials and Observations ,Adenine ,Hematology ,Lymphoma, B-Cell, Marginal Zone ,Cohort Studies ,Pyrimidines ,Treatment Outcome ,Oncology ,Piperidines ,Humans ,Pyrazoles ,Neoplasm Recurrence, Local ,Molecular Biology - Abstract
Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: “ibrutinib responders”—patients who achieved complete or partial response (CR/PR) to ibrutinib; “stable disease (SD)”; and “primary progressors (PP)”—patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23–7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03–8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17–37.62, p p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.
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- 2022
16. <scp>R‐MACLO‐IVAM</scp> regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma ‐ Long term follow up results
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Isildinha M. Reis, Izidore S. Lossos, Eduardo Edelman Saul, Joseph D. Rosenblatt, Alvaro J. Alencar, Juan Pablo Alderuccio, and Sunil Iyer
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Kaplan-Meier Estimate ,Lymphoma, Mantle-Cell ,Gastroenterology ,Disease-Free Survival ,Maintenance Chemotherapy ,Young Adult ,Maintenance therapy ,Median follow-up ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Ifosfamide ,Prospective Studies ,Adverse effect ,Cyclophosphamide ,Aged ,Etoposide ,Aged, 80 and over ,Not evaluated ,business.industry ,Remission Induction ,Cytarabine ,Hematology ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Thalidomide ,Regimen ,Methotrexate ,Doxorubicin ,Vincristine ,Female ,Mantle cell lymphoma ,Rituximab ,business ,Follow-Up Studies ,medicine.drug - Abstract
We present long-term combined results of two clinical trials implementing R-MACLO-IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM-MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM-MCL2 ClinicalTrials.gov identifier NCT00878254) received rituximab (375 mg/m2 IV weekly × 4, repeated every 6 months for 3 years). Considering all 44 patients, 41 (93.2%) achieved complete response (CR), two (4.5%) partial response (PR), and one (2.3%) was not evaluated for response. With a median follow up of 7.2 years (range < 1 month to 16 years), the 5-year progression-free survival (PFS) was 55.6% (95% CI: 38.9%-69.4%) and median PFS 7.9 years (95% CI: 3.7-11 years). The 5-year OS was 83.3% (95% CI: 68.1%-91.7%) and median OS was not reached. Patients with blastic variant (n = 6) had a 5-year PFS and OS of 20.8% and 60%, respectively. Myelosuppression was the most common adverse event during immunochemotherapy. Long-term treatment-related mortality was 6.8%. Note, R-MACLO-IVAM followed by maintenance therapy is an effective regimen to induce long-term remission in MCL without need for consolidation with ASCT.
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- 2021
17. Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study
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Craig A. Portell, Seo-Hyun Kim, Catherine Wei, Neil Palmisiano, Catherine Diefenbach, Manali Kamdar, Madelyn Burkart, Nadia Khan, Seth M. Maliske, Izidore S. Lossos, Andreas K. Klein, Paolo Caimi, Narendranath Epperla, Amandeep Godara, Alexey V. Danilov, Victor M. Orellana-Noia, Max J. Gordon, Adam Zayac, Maryam Sarraf Yazdy, Allandria Straker-Edwards, Michael C. Churnetski, Ayushi Chauhan, Umar Farooq, Deepa Jagadeesh, Daulath Singh, Matthew A. Lunning, Suchitra Sundaram, Sarah Stettner, Kirsten M Boughan, Lori A. Leslie, Yusra F. Shao, Peter Martin, Amy Sperling, Stephen D. Smith, Reem Karmali, Bradley M. Haverkos, Parameswaran Venugopal, Veronika Bachanova, Tycel Phillips, Yun Kyong Choi, Malvi Savani, Seema Naik, Gaurav Varma, Vaishalee P. Kenkre, Gabriella Magarelli, Ryan Vaca, Asaad Trabolsi, Andrew M. Evens, Juan Pablo Alderuccio, Emma Rabinovich, Christopher D'Angelo, Nishitha Reddy, Adam J. Olszewski, Kristie A. Blum, Stephanie Berg, David A. Bond, and Kevin A. David
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Oncology ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Hematology ,medicine.disease ,Lower risk ,Lymphoma ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Cumulative incidence ,Young adult ,business ,030215 immunology ,Cohort study - Abstract
Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P
- Published
- 2021
18. Current Treatments in Marginal Zone Lymphoma
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Juan Pablo, Alderuccio and Brad S, Kahl
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Incidence ,Positron Emission Tomography Computed Tomography ,Humans ,Lymphoma, B-Cell, Marginal Zone ,Lymphoma, Follicular - Abstract
Marginal zone lymphoma (MZL) is a heterogenous group of indolent non-Hodgkin lymphomas (NHLs). Three subtypes are recognized based on the site of involvement: extranodal MZL, splenic MZL, and nodal MZL. MZL represents 7% of all mature NHLs that exhibit geographical variability in their incidence and association with infectious agents. Each MZL subtype is characterized by unique biology, clinical presentation, therapeutic approach, and natural history. Recent findings have improved risk stratification of patients at diagnosis and after frontline therapy; however, these data are not incorporated into treatment decisions or selections of therapeutic agents. Moreover, a limited number of patients with MZL have been enrolled in randomized clinical trials, and all subtypes have been analyzed as a single group. This approach precludes a full characterization of the efficacy of treatment platforms, and current recommendations are largely derived from experience with follicular lymphoma. Emerging data have demonstrated that novel agents have higher efficacy and safety, expanding the landscape of treatment options. However, despite recent advances, several unmet needs remain in this field, including the discovery of prognostic biomarkers, utility of PET/CT at different extranodal sites, and appropriate sequence of therapies. There is a significant need to design clinical trials with the power to establish standard therapies as well as to assess their effects on patient-reported outcomes. In this review, we will provide an updated analysis of the literature and discuss our approach to the diagnosis and treatment of patients with MZL.
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- 2022
19. Long-term outcomes of frontline 90Y-ibritumomab tiuxetan in marginal zone lymphoma
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Joseph D. Rosenblatt, Izidore S. Lossos, Isildinha M. Reis, and Juan Pablo Alderuccio
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Marginal zone lymphoma ,Hematology ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Localized disease ,Long term outcomes ,medicine ,90Y ibritumomab tiuxetan ,business ,030215 immunology - Abstract
The best upfront therapy for patients with non-gastric extranodal marginal zone lymphoma (EMZL) remains unclear. Patients with localized disease are usually treated with radiation therapy resulting...
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- 2020
20. Clinical and radiological characteristics of patients with pulmonary marginal zone lymphoma: A single center analysis
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Muhammad Husnain, Wei Zhao, Sunil Iyer, Isildinha M. Reis, Juan Pablo Alderuccio, Francisco Vega, Izidore S. Lossos, Jennifer R. Chapman, and Russ Kuker
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Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Marginal zone lymphoma ,radiographic findings ,treatment outcomes ,Disease ,Single Center ,lcsh:RC254-282 ,Gastroenterology ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pulmonary marginal zone lymphoma ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Original Research ,Aged, 80 and over ,Lung ,business.industry ,Clinical Cancer Research ,Lymphoma, B-Cell, Marginal Zone ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Lymphoma ,Radiation therapy ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,B symptoms ,030220 oncology & carcinogenesis ,Radiological weapon ,Female ,medicine.symptom ,business - Abstract
Pulmonary marginal zone lymphoma (PMZL) is the most common non‐Hodgkin lymphoma affecting the lung. PMZL is usually an indolent disease. Clinical and radiological variables associated with shorter survival are largely unknown and no consensus exists on preferred treatment strategy in PMZL. Herein we aimed to identify clinical and radiological features associated with shorter survival and inferior treatment outcomes. Forty patients with PMZL were analyzed. FDG‐avid disease was evident in most patients (93%) with staging PET/CT (n = 15). With a median follow‐up in treated patients (n = 38) of 8.4 years (range 0.07‐18.44), the median progression‐free survival (PFS) and overall survival (OS) were 7.5 years (95% CI 1.8‐9.5) and 15.7 years (95% CI 9.3‐NE) respectively. Shorter PFS was observed in patients who presented at diagnosis with elevated LDH, B symptoms, advanced stage and failed to achieve complete response (CR) after initial treatment. Patients with multifocal lung disease, extrapulmonary MZL and cavitary lesions on CT scans exhibited shorter PFS. Nevertheless, no clinical or radiologic findings were associated with shorter OS. All patients treated with surgery (n = 4) and radiation therapy (n = 3) achieved and remained in CR. No higher grade transformations occurred during the follow‐up period. PMZL exhibited excellent outcomes with a 15‐year PMZL‐related OS of 94.9% (95% CI: 81.25%‐98.7%). Radiation therapy and surgery are potentially curative strategies in localized PMZL., Elevated LDH, B symptoms, advanced stage and failure to achieve complete response after initial treatment are clinical variables associated with shorter progression‐free survival (PFS) in pulmonary marginal zone lymphoma (PMZL). Multifocal lung disease, extrapulmonary MZL and cavitary lesions on computed tomography scans have been identified as radiologic features associated with shorter PFS. Radiation therapy and surgery are potentially curative strategies in PMZL.
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- 2020
21. Diagnostic bone marrow biopsy in patients with stage I EMZL treated with radiation therapy: needed or not?
- Author
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Derek Isrow, Juan Pablo Alderuccio, Wei Zhao, Jennifer R. Chapman, Sunil Iyer, Jessica Meshman, Arnold M. Markoe, Izidore S. Lossos, Isildinha M. Reis, and Francisco M. Vega
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Male ,medicine.medical_specialty ,Biopsy ,medicine.medical_treatment ,Immunology ,MEDLINE ,Biochemistry ,Text mining ,Bone Marrow ,Humans ,Medicine ,In patient ,Letter to Blood ,Aged ,Neoplasm Staging ,medicine.diagnostic_test ,business.industry ,Lymphoma, B-Cell, Marginal Zone ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Lymphoma ,Radiation therapy ,medicine.anatomical_structure ,Female ,Radiology ,Bone marrow ,business - Published
- 2020
22. Marginal zone lymphoma of the colon: case series from a single center and SEER data review
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Asaad Trabolsi, Juan Pablo Alderuccio, Jorge Florindez, Gregor Rodriguez, Eduardo Saul, Sunil Girish Iyer, Jennifer R. Chapman, Julio Poveda, Daniel A. Sussman, and Izidore S. Lossos
- Subjects
Cohort Studies ,Male ,Cancer Research ,Oncology ,Colon ,Humans ,Hematology ,Lymphoma, B-Cell, Marginal Zone ,Prognosis ,Retrospective Studies - Abstract
Colon extranodal marginal zone lymphoma (EMZL) is poorly characterized in the literature. We performed a retrospective review of patients with colon EMZL at our institution and from the Surveillance Epidemiology and End Results (SEER) database. Eight patients were identified in our institution with majority (88%) presenting with stage-I disease. Initial management included active surveillance, polypectomy followed by surveillance, and surgical resection followed by chemotherapy. One patient with concurrent prostate carcinoma received radiation to the rectum. Initial therapy led to complete remission in five out of six treated patients with four of them maintaining remission at 88 months. SEER database identified 361 patients with stage-I colon EMZL. Overall survival for this cohort was 73.9% at 10 years with no significant difference in outcomes between treatment groups. Our single institution experience and the SEER data analysis emphasize indolent nature of colon EMZL and need for non-aggressive therapeutic approaches.
- Published
- 2021
23. ABCs of ADCs in management of relapsed/refractory diffuse large B-cell lymphoma
- Author
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Juan Pablo, Alderuccio and Jeff P, Sharman
- Subjects
Immunoconjugates ,Receptors, Chimeric Antigen ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,Cytotoxins ,Lymphoma, Non-Hodgkin ,Humans ,Antibodies, Monoclonal ,Lymphoma, Large B-Cell, Diffuse ,Hematology ,Neoplasm Recurrence, Local ,Karyopherins - Abstract
In the past 5 years, 3 chimeric antigen receptor (CAR) T-cell therapies, 2 antibody-drug conjugates (ADCs), 1 CD19-directed monoclonal antibody, and 1 exportin-1 inhibitor have been approved by the Food and Drug Administration for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The noncellular therapies received accelerated approval based on the overall response rate in clinical trials that differ in multiple aspects of the patient populations enrolled, including age, performance status, prior lines of therapy, and inclusion of patients with primary refractory DLBCL, transformed lymphoma, or high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6. ADCs approved for DLBCL differ in target antigen, antibody structure, linker, and cytotoxin, which results in a different safety and efficacy profile. Here, we comprehensively review the current knowledge of recently approved and emerging strategies for the management of R/R DLBCL with a focus on ADCs.
- Published
- 2022
24. A single-center analysis of patients with extranodal marginal zone lymphoma of the breast
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Jennifer R. Chapman, Juan Pablo Alderuccio, Jorge A. Florindez, Eduardo Edelman Saul, Russ Kuker, Asaad Trabolsi, Gregor A. Rodriguez, Sunil Iyer, and Izidore S. Lossos
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hematology ,Disease ,Lymphoma, B-Cell, Marginal Zone ,Single Center ,Malignancy ,medicine.disease ,Occult ,Radiation therapy ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Positron Emission Tomography Computed Tomography ,medicine ,Humans ,Radiology ,Bone marrow ,Progression-free survival ,Stage (cooking) ,business ,Retrospective Studies - Abstract
Breast extranodal marginal zone lymphoma (EMZL) is a rare malignancy. We performed the largest published to date single-center retrospective analysis of 13 patients with breast EMZL focusing on clinical characteristics and treatment-related outcomes. The rarity of this disease at our center was concordant with the prevalence reported in the literature, with breast EMZL comprising 2% of 654 MZL cases. Most patients presented with stage I-II disease however four (30.8%) patients had stage IV disease mostly due to occult bone marrow (BM) involvement. Interestingly, EMZL was frequently non-FDG avid (66.7%) on staging PET/CT. With a median follow-up of 3.1 years (range 5 months to 10.2 years), the 3-year progression free survival was 68.7% (95%CI 30.2%-88.9%) and overall survival 80.2% (95%CI 40.3%-94.8%). No patient experienced higher-grade transformation. Herein we show that localized breast EMZL can be effectively treated with radiation therapy providing long term disease control.
- Published
- 2021
25. NOTCH signaling in the pathogenesis of splenic marginal zone lymphoma-opportunities for therapy
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Juan Pablo Alderuccio and Izidore S. Lossos
- Subjects
Cancer Research ,Lymphoma ,Splenic Neoplasms ,Druggability ,Regulator ,Notch signaling pathway ,Hematology ,Disease ,Lymphoma, B-Cell, Marginal Zone ,Biology ,medicine.disease ,Marginal zone ,Leukemia, Lymphocytic, Chronic, B-Cell ,Pathogenesis ,Oncology ,Mutation ,Cancer research ,medicine ,Biomarker (medicine) ,Humans ,Splenic marginal zone lymphoma ,Signal Transduction - Abstract
NOTCH signaling is a highly conserved pathway mediated by four receptors (NOTCH 1-4) playing critical functions in proliferation, differentiation, and cell death. Under physiologic circumstances, NOTCH2 is a key regulator in marginal zone differentiation and development. Over the last decade, growing data demonstrated frequent NOTCH2 mutations in splenic marginal zone lymphoma (SMZL) underscoring its critical role in the pathogenesis of this disease. Moreover, NOTCH2 specificity across studies supports the rationale to assess its value as a diagnosis biomarker in a disease without pathognomonic features. These data make NOTCH signaling an appealing target for drug discovery in SMZL; however, prior efforts attempting to manipulate this pathway failed to demonstrate meaningful clinical benefit, or their safety profile prevented further development. In this review, we discuss the current knowledge of NOTCH implications in the pathogenesis and as a potential druggable target in SMZL.
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- 2021
26. A Multi-Center, Open Label, Phase I/II Study to Assess the Safety and Efficacy of Tenalisib Given in Combination with Romidepsin in Patients with Relapsed/Refractory T-Cell Lymphoma
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Don A. Stevens, Suchitra Sundaram, Swami P. Iyer, Auris Huen, Mary Jo Lechowicz, Weiyun Z. Ai, Tatyana Feldman, Craig Okada, Juan Pablo Alderuccio, Ann Mohrbacher, Bradley M. Haverkos, Timothy M. Kuzel, Ajit Nair, Kasi V. Routhu, Deepa Jagadeesh, Ryan A. Wilcox, Prajak J Barde, and Nishitha Reddy
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Romidepsin ,Phase i ii ,Internal medicine ,Relapsed refractory ,medicine ,T-cell lymphoma ,In patient ,Center (algebra and category theory) ,Open label ,business ,health care economics and organizations ,medicine.drug - Abstract
Background: T cell lymphomas (TCL) have been known to exhibit epigenetic dysregulation and aberrant cell signaling. Tenalisib (RP6530), a highly selective PI3K δ/γ+SIK3 inhibitor has shown clinically promising activity as a single agent in TCL with a differentiated and favorable safety profile. In vitro studies in TCL cell lines showed increased apoptosis when tenalisib was combined with romidepsin (Rhizen data on file). A Phase I/II study of tenalisib in combination with romidepsin was designed to assess safety, pharmacokinetics and efficacy in relapsed/refractory TCL (NCT03770000). Methods: This is a multi-center, open label, Phase I/II study in patients with T cell lymphoma (PTCL and CTCL). The Phase I is a 3+3 dose escalation study to determine the MTD/optimal dose. The Phase II is an expansion cohort at the MTD/optimal dose of the combination. Tenalisib was administered orally at doses of 400, 600 and 800 mg BID in combination with romidepsin (12 &14 mg/m2, Q3W). The objectives of the study are to establish safety, MTD/optimal dose, pharmacokinetics and anti-tumor activity of the combination. We report the dose escalation results and preliminary data from the expansion cohorts. Results: A total 15 patients were enrolled between July 24, 2019 and July 20, 2020. Baseline demographics are presented in Table 1. Patients had a median of 3 (range; 1-17) prior treatments and 11 (73%) were refractory to their last therapy. About 67% (6/9) of CTCL patients had prior mogamulizumab therapy. No DLT was reported in the dose escalation phase and Tenalisib 800 mg BID+ Romidepsin 14 mg/m2, Q3W was considered as the optimal dose for expansion cohorts. PK analysis showed linear and dose-dependent kinetics for tenalisib. Co-administration of romidepsin along with tenalisib did not significantly alter the mutual PK of either agents. Fifteen patients were assessed for safety. Most common treatment emergent adverse events of any grade were nausea (33%), thrombocytopenia (33%) and fatigue (27%). Related ≥ Grade 3 AEs were seen in 5 (33%) patients. These included thrombocytopenia (7%), atrial fibrillation (7%) and pyrexia (7%) which were related to romidepsin while anemia (7%) neutropenia (7%) and rash (7%) were considered related to the combination. There were no instances of transaminitis or colitis. None of the TEAEs led to study discontinuation. Patients from the dose escalation cohorts (n=9) were evaluated for response. Three patients (3/9) showed complete response (CR), 4 patients (4/9) showed stable disease (SD) while 2 patients (2/9) had progressive disease (PD). Out of the three responders, two were PTCL (AITL) patients, one of which is planned for transplantation, while the third patient was a CTCL (Sezary syndrome) patient who had progressed on prior mogamulizumab therapy. This patient showed rapid reduction of Sezary cell count after 2 cycles of treatment. Three patients (2 CR, 1 SD) are currently ongoing with a median duration of response being 9.0 (range; 7.6-10.5+) months. The expansion cohort has 6 patients and is currently enrolling. Conclusions: The combination of tenalisib and romidepsin demonstrates a favorable safety profile and promising indicators of combined anti-tumour activity in patients with R/R TCL. The expansion cohort in CTCL and PTCL is currently underway to validate these encouraging early results. Updated results will be presented during the ASH meeting. Disclosures Iyer: Afffimed: Research Funding; Rhizen: Research Funding; Seattle Genetics, Inc.: Research Funding; Curio Biosciences: Honoraria; Trillium: Research Funding; Daiichi Sankyo: Consultancy; Legend Biotech: Consultancy; Target Oncology: Honoraria; Spectrum: Research Funding; Merck: Research Funding; CRISPR: Research Funding. Huen:Seattle Genetics: Consultancy, Research Funding; Kyowa Kirin: Consultancy, Research Funding; Rhizen: Research Funding; Glaxo Smith Kline: Research Funding; Galderma: Research Funding; Miragen: Research Funding; Helsinn: Consultancy; Medivir: Research Funding. Haverkos:Viracta THerapeutics: Consultancy. Ai:ADC Therapeutics, Kymera: Membership on an entity's Board of Directors or advisory committees; Nurix Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kuzel:Eselixis, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genomic Health: Honoraria; Sanofi/Genzyme: Honoraria; Bioarray: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Marck: Membership on an entity's Board of Directors or advisory committees; Tyme: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; OncLive: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Feldman:Viracta: Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Trillium: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Cell Medica: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Takeda: Honoraria, Other: Travel expenses; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Eisai: Research Funding. Jagadeesh:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Debiopharm Group: Research Funding; MEI Pharma: Research Funding. Reddy:KITE Pharma, Abbvie, BMS, Celgene: Consultancy; Genentech, BMS: Research Funding. Routhu:Rhizen Pharmaceuticals S.A>.: Current Employment. Barde:Rhizen Pharmaceuticals S.A: Current Employment. Nair:Rhizen Pharmaceuticals S.A.: Current Employment.
- Published
- 2020
27. Efficacy and Safety of Loncastuximab Tesirine (ADCT-402) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Author
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Brian T. Hess, Pier Luigi Zinzani, Kirit M. Ardeshna, John Radford, Mehdi Hamadani, Brad S. Kahl, Anastasios Stathis, David Ungar, Yajuan Qin, Weiyun Z. Ai, Shui He, Melhem Solh, Paolo Caimi, Juan Pablo Alderuccio, Jay Feingold, and Carmelo Carlo-Stella
- Subjects
business.industry ,Immunology ,Relapsed refractory ,Cancer research ,Medicine ,Cell Biology ,Hematology ,business ,medicine.disease ,Biochemistry ,Diffuse large B-cell lymphoma - Abstract
Introduction: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who fail multi-agent chemoimmunotherapy have a poor prognosis and a need for more treatment options. Loncastuximab tesirine (Lonca) comprises a humanized anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin. We present updated results from a phase 2 study of Lonca in patients with R/R DLBCL who had failed established therapies, including analysis of response in high-risk DLBCL subgroups. Methods: Patients aged ≥18 years with R/R DLBCL who had failed ≥2 prior therapies were enrolled in this single-arm open-label phase 2 study (NCT03589469). Overall response rate (ORR) was assessed by independent reviewer according to the Lugano response criteria and duration of response (DoR) was defined as the time from earliest date of first response until the first date of either disease progression or death due to any cause. Pre-specified analyses of ORR and DoR by demographic and clinical characteristics were performed. Treatment-emergent adverse events (TEAEs) were reported for the all-treated population and by age group. Results: In this study, 145 patients with DLBCL received Lonca (mean 4.3 cycles [range: 1-15]) and were evaluable for safety and efficacy. As of data cutoff (April 6, 2020), follow-up was ≥6 months since first dose. The ORR was 48.3%, and complete response rate (CRR) was 24.1%. Median DoR (mDoR) for the 70 responders was 10.3 months. For patients with a CR, mDoR was 13.4 months (Figure 1). Most patients responded after 2 treatment cycles; median time to first response was 41.0 days. Responses, including CRs, were observed in several subgroups with higher-risk characteristics (Figure 2). ORR was 44.8% in patients with transformed disease, 45.8% in patients aged 65-74 years, and 52.4% in patients aged ≥75 years. For patients with double- or triple-hit DLBCL, ORR was 33.3% (notably all CRs). Patients who were refractory (no response) to first-line therapy, most recent therapy, or any prior therapy had ORRs of 37.9%, 36.9%, and 36.0%, respectively. Patients who had received a prior stem cell transplant (SCT) had a notable ORR of 58.3%. Lonca was also effective in patients who had received prior CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy (ORR 46.2%). Durable responses were noted in patients with high-risk characteristics. mDoR was not reached for patients with transformed disease. Older patients had a longer mDoR than younger patients ( Following Lonca treatment, 15 patients received CD19-directed CAR-T therapy with an investigator-assessed ORR of 46.7% (6 CR; 1 partial response), and 9 patients proceeded to SCT as consolidation after responding to Lonca. Overall, 143 (98.6%) patients had ≥1 TEAE and 105 (72.4%) patients had grade ≥3 TEAEs. The most common (≥25%) all-grade TEAEs were gamma-glutamyltransferase (GGT) increased (40.7%), neutropenia (39.3%), thrombocytopenia (33.1%), fatigue (27.6%), and anemia (26.2%). The most common (≥10%) grade ≥3 TEAEs were neutropenia (25.5%), thrombocytopenia (17.9%), GGT increased (16.6%), and anemia (10.3%). Treatment-related TEAEs leading to treatment discontinuation occurred in 24 patients (16.6%), most commonly GGT increased (14 patients; 9.7%). No increase in toxicity was seen in patients aged ≥65 years compared with younger patients. Conclusions: Lonca had substantial single-agent antitumor activity in patients with R/R DLBCL. No new safety concerns were identified and no increase in toxicity was observed for patients aged ≥65 years. Encouraging and durable responses were observed in high-risk patient groups, including double- or triple-hit, transformed or refractory DLBCL, and notably in those who had progressed after prior CAR-T cell therapy. In addition, investigator-reported ORR indicates that many patients also respond to CAR-T therapy given after Lonca. Updated DoR data will be presented at the meeting. Funding: This study is sponsored by ADC Therapeutics SA; clinicaltrials.gov/ct2/show/NCT03589469. Disclosures Caimi: Celgene: Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech, ADC Therapeutics: Research Funding; ADCT, Kite Therapeutics, Genentech, Amgen, Verastem, TG Therapeutics, Bayer: Consultancy. Ai:ADC Therapeutics, Kymera: Membership on an entity's Board of Directors or advisory committees; Nurix Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Puma Biotechnology: Other: Family member; Foundation Medicine: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member. Ardeshna:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi, Genzyme, AstraZeneca: Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; University College London (UCL)/UCL Hospitals (UCLH) Biomedical Research Unit: Other: Supported by this organisation; Beigene: Membership on an entity's Board of Directors or advisory committees. Hamadani:Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Janssen R&D; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio: Consultancy; Sanofi Genzyme, AstraZeneca: Speakers Bureau. Hess:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kahl:Roche Laboratories Inc: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics LLC: Consultancy. Radford:GlaxoSmithKline: Current equity holder in publicly-traded company, Other: Spouse; AstraZeneca: Current equity holder in publicly-traded company, Other: Spouse; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Research Funding; ADCT: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stathis:Member of the steering committee of the trial of this abstract: Other; Loxo: Honoraria, Other, Research Funding; Cellestia: Research Funding; PharmaMar: Other: Travel Grant; Abbvie: Other: Travel Grant; ADC Therapeutcis: Other, Research Funding; MEI Pharma: Other, Research Funding; Novartis: Other, Research Funding; Bayer: Other, Research Funding; Merck: Other, Research Funding; Roche: Other, Research Funding; Pfizer: Other, Research Funding. Zinzani:Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau. Feingold:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Ungar:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Qin:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. He:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Carlo-Stella:Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; Boehringer Ingelheim and Sanofi: Consultancy.
- Published
- 2020
28. Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma
- Author
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Brian Hess, William Townsend, Weiyun Ai, Anastasios Stathis, Melhem Solh, Juan Pablo Alderuccio, David Ungar, Sam Liao, Lori Liao, Lisa Khouri, Xiaoyan Zhang, and Joseph Boni
- Subjects
Benzodiazepines ,Immunoconjugates ,Treatment Outcome ,Pharmaceutical Science ,Humans ,Kaplan-Meier Estimate ,Lymphoma, Large B-Cell, Diffuse ,Antibodies, Monoclonal, Humanized - Abstract
We developed an integrated population pharmacokinetic model to investigate loncastuximab tesirine pharmacokinetics (PK) and exposure-response relationships for relapsed/refractory B cell non-Hodgkin lymphoma, including diffuse large B cell lymphoma (DLBCL). The model, based on the recommended dosing schedule (150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W thereafter) and drug concentrations in phase 1 and 2 studies (DLBCL [n = 284], non-DLBCL [n = 44]), was used to characterize loncastuximab tesirine PK and evaluate exposure covariates. Relationships between exposure (pyrrolobenzodiazepine-conjugated antibody [cAb] cycle 1 average concentration) and (1) efficacy (including overall response rate [ORR; primary endpoint] and overall survival [OS]) and (2) grade ≥ 2 treatment-emergent adverse events were explored. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression. cAb and total Ab were best described by a two-compartment linear model with time-dependent clearance. The cAb steady-state half-life increased to 20.6 days by ~ 15 weeks. cAb exposure was lower for low albumin, mild/moderate hepatic impairment, non-DLBCL subtypes, and Eastern Cooperative Oncology Group scores 1. Significant positive associations were reported between exposure and ORR (p = 3.21E-6), OS (p = 0.0016), grade ≥ 2 increased gamma-glutamyltransferase, liver function test abnormalities, pain, and skin/nail reactions (p 0.05). Low albumin, bulky disease, and mild/moderate hepatic impairment had a significant negative effect on OS (p 0.01). Modeling supports the recommended loncastuximab tesirine dosing schedule. Although reduced exposure and efficacy were predicted for specific covariates (e.g., low albumin, mild/moderate hepatic impairment), dose increases are not recommended. Trial registration: NCT02669017 and NCT03589469.
- Published
- 2021
29. LOTIS 2 FOLLOW‐UP ANALYSIS: UPDATED RESULTS FROM A PHASE 2 STUDY OF LONCASTUXIMAB TESIRINE IN RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA
- Author
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Carmelo Carlo-Stella, Juan Pablo Alderuccio, Mehdi Hamadani, Brad S. Kahl, John Radford, Brian T. Hess, Yajuan Qin, Shui He, Anastasios Stathis, P. L. Zinzani, David Ungar, Jay Feingold, W. Y. Ai, Melhem Solh, Kirit M. Ardeshna, and Paolo Caimi
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Phases of clinical research ,Refractory Diffuse Large B-Cell Lymphoma ,Hematology ,General Medicine ,Radiology ,business - Published
- 2021
30. Unusual Variants of Follicular Lymphoma
- Author
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Yao Shan Fan, Jing Hong Peng, Daniel P. Cassidy, Khaled Algashaamy, Mahsa Khanlari, Sandra Sanchez, Jessica P. Alvarez, Francisco Vega, Juan Pablo Alderuccio, Kyle White, Jennifer R. Chapman, Izidore S. Lossos, and Alvaro J. Alencar
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Follicular lymphoma ,Disease ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,Lymphoma, Follicular ,Grading (tumors) ,Aged ,Aged, 80 and over ,biology ,CD23 ,Middle Aged ,medicine.disease ,Marginal zone ,Lymphoma ,030104 developmental biology ,Lymphatic system ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Surgery ,Anatomy ,Antibody - Abstract
Follicular lymphoma (FL) is one of the most frequently diagnosed lymphomas in the United States and Europe. The definition of and basic approach to diagnosis and grading of FL is essentially unchanged in the recently updated revision of the World Health Organization (WHO) classification. FL is a biologically and histopathologically heterogeneous disease. Although there is an improved understanding of some FL variants and specific subtypes, there are cases whose recognition is particularly challenging, either because they have unusual features or represent examples of new or rare variants. Herein, we share a series of unusual and difficult to recognize FLs with the goal of increasing awareness of the expanding histopathologic variability in FL. Unusual FL discussed here include: FL with Castleman-like changes, FL with plasmacytic differentiation, and immunoglobulin G4-positive plasma cells in the setting of immunoglobulin G4-related disease, FL with marginal zone differentiation and involving mucosa-associated lymphoid tissue sites, diffuse FL variant expressing CD23 with STAT6 mutation, large B-cell lymphoma with IRF4 rearrangement, CD10-negative and MUM1-positive aggressive FL, and Epstein-Barr virus-positive FL.
- Published
- 2019
31. Central nervous system emergencies in haematological malignancies
- Author
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Macarena I. de la Fuente, Juan Pablo Alderuccio, and Izidore S. Lossos
- Subjects
medicine.medical_specialty ,Central nervous system ,Status epilepticus ,Disease course ,03 medical and health sciences ,Status Epilepticus ,0302 clinical medicine ,Spinal cord compression ,medicine ,Humans ,Elevated Intracranial Pressure ,Intensive care medicine ,business.industry ,Hematology ,medicine.disease ,Neurovascular bundle ,Pathophysiology ,medicine.anatomical_structure ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Intracranial Hypertension ,medicine.symptom ,business ,Spinal Cord Compression ,030215 immunology - Abstract
Neurological emergencies are frequently catastrophic events in the course of haematological malignancies (HM) that, if not promptly recognized and treated, may lead to lethal outcomes or chronic sequelae. They may occur at any time during the disease course, but are more frequently observed following relapse. Practice guidelines are lacking in the management of most central nervous system (CNS) complications in HM. Herein we review the pathophysiology, presentation and treatment of elevated intracranial pressure, spinal cord compression, status epilepticus, neurovascular complications, CNS infection, leucostasis and hyperviscosity. Further, we discuss the expanding spectrum of neurological complications of old and novel treatments in HM.
- Published
- 2019
32. Maintenance rituximab or observation after frontline treatment with bendamustine‐rituximab for follicular lymphoma
- Author
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Melody R. Becnel, Andrew M. Evens, Stephen D. Smith, Pooja Mehra, Amrita Desai, Prathima Reddy, Dhruvika Mukhija, Max L. Goldman, Bita Fakhri, James R. Cerhan, Brad S. Kahl, Abhigna Kodali, Jonathon B. Cohen, Brian K. Link, Juan Pablo Alderuccio, Deepa Jagadeesh, Nilanjan Ghosh, Allison M. Winter, Izidore S. Lossos, Thomas M. Habermann, Mohammad Junaid Hussain, Oscar Calzada, Timothy Tiutan, Peter Martin, Loretta J. Nastoupil, Craig A. Portell, Matthew J. Maurer, Brian T. Hill, and Paolo Caimi
- Subjects
Male ,Oncology ,Lymphoma ,Follicular lymphoma ,Cardiorespiratory Medicine and Haematology ,chemistry.chemical_compound ,rituximab ,0302 clinical medicine ,Prednisone ,Obinutuzumab ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Bendamustine Hydrochloride ,Lymphoma, Follicular ,Cancer ,Aged, 80 and over ,Hematology ,Middle Aged ,Survival Rate ,Tolerability ,Vincristine ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Female ,Rituximab ,medicine.drug ,Adult ,Bendamustine ,medicine.medical_specialty ,Cyclophosphamide ,Immunology ,Disease-Free Survival ,Article ,maintenance ,Maintenance Chemotherapy ,03 medical and health sciences ,Rare Diseases ,follicular lymphoma ,Clinical Research ,Internal medicine ,medicine ,Humans ,bendamustine ,Aged ,Retrospective Studies ,business.industry ,Follicular ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,chemistry ,Doxorubicin ,business ,030215 immunology - Abstract
Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.
- Published
- 2018
33. Risk Factors for Transformation to Higher-Grade Lymphoma and Its Impact on Survival in a Large Cohort of Patients With Marginal Zone Lymphoma From a Single Institution
- Author
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Nicolas Gallastegui, Jeremy Ramdial, Francisco M. Vega, Joseph D. Rosenblatt, Amrita Desai, Juan Pablo Alderuccio, Isildinha M. Reis, Wei Zhao, Macarena I. de la Fuente, Erik Kimble, Jennifer R. Chapman, and Izidore S. Lossos
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Marginal zone lymphoma ,Complete remission ,Aggressive lymphoma ,medicine.disease ,Lymphoma ,Large cohort ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Cox proportional hazards regression ,Medicine ,In patient ,Single institution ,business ,030215 immunology - Abstract
Purpose Given the paucity of data on higher-grade transformation (HGT) to aggressive lymphoma in patients with marginal zone lymphoma (MZL), we report on a large cohort of patients, identify risk factors, and determine HGT impact on overall survival (OS). Methods We analyzed 453 patients with biopsy-proven MZL seen at our institution between 1995 and 2016. Kaplan-Meier, Cox proportional hazards regression, and competing risk methods were used in analyses of time-to-event outcomes. Results Thirty-four patients (7.5%) had biopsy-proven HGT to diffuse large B-cell lymphoma, including seven (21%) diagnosed at the time of initial MZL diagnosis. Among 27 incident patients, median time to HGT was 29 months (range, 1.3 to 135 months). Higher risk of HGT was observed in those with nodal/splenic MZL (subdistribution hazard ratio [SHR], 2.60; P = .023). On multivariable competing risk analysis, elevated lactate dehydrogenase (SHR, 2.71), more than four nodal sites (SHR, 2.97), and failure to achieve complete remission (CR) after initial treatment (SHR, 3.76) conveyed significantly higher risk for HGT ( P < .02). International Prognostic Index (IPI), Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were only significant predictors of HGT univariably. Patients with HGT had shorter OS (5-year rate, 65% v 86%; P < .001). Patients who presented with HGT within 12 months since MZL diagnosis had shorter OS than those with HGT at MZL diagnosis combined with those with HGT more than 12 months later (4-year rate, 43% v 81%, P < .001). Non-CR and higher scores of IPI, Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were the main significant predictors for shorter progression-free survival and OS. Conclusion Failure to achieve CR after initial treatment, elevated lactate dehydrogenase, and more than four nodal sites at the time of MZL diagnosis are the main predictors of increased risk of HGT. Patients with HGT have shorter OS.
- Published
- 2018
34. HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis
- Author
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Madelyn Burkart, Nishitha Reddy, Suchitra Sundaram, Victor M. Orellana-Noia, Adam Zayac, Andrew M. Evens, Andreas K. Klein, Alessia Dalla Pria, Catherine Diefenbach, Ayushi Chauhan, Kristie A. Blum, Umar Farooq, Frank A. Post, Stephanie Berg, Michael C. Churnetski, Graham P. Collins, Deepa Jagadeesh, Agrima Mian, Alexey V. Danilov, David A. Bond, Yun Kyong Choi, Seema Naik, Vaishalee P. Kenkre, Scott E. Smith, Kirsten M Boughan, Craig A. Portell, Yong Lin, Seth M. Maliske, Izidore S. Lossos, Tatyana Feldman, Andrzej Stadnik, Adam J. Olszewski, Stephen D. Smith, Amandeep Godara, Gaurav Varma, Shireen Kassam, Peter Martin, Christopher D'Angelo, Mark Bower, Albert Ren, Reem Karmali, Narendranath Epperla, Bradley M. Haverkos, Silvia Montoto, Parameswaran Venugopal, Manali Kamdar, Nadia Khan, Kate Cwynarski, Maryam Sarraf Yazdy, Juan Pablo Alderuccio, Catherine Zhu, Amy Sperling, Seo-Hyun Kim, Ryan Vaca, Emma Rabinovich, Daniel Rector, Allandria Straker-Edwards, Catherine Wei, and Paolo Caimi
- Subjects
Oncology ,medicine.medical_specialty ,Vincristine ,Cyclophosphamide ,Clinical Trials and Observations ,HIV Infections ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Median follow-up ,Internal medicine ,Medicine ,Humans ,Etoposide ,Ifosfamide ,business.industry ,Hematology ,medicine.disease ,Burkitt Lymphoma ,United Kingdom ,United States ,Lymphoma ,030220 oncology & carcinogenesis ,Cytarabine ,Neoplasm Recurrence, Local ,business ,Rituximab ,Burkitt's lymphoma ,030215 immunology ,medicine.drug - Abstract
Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.
- Published
- 2021
35. ABCL-362: Incidence, Onset, and Management of Myelosuppression in Patients Treated with loncastuximab Tesirine for R/R DLBCL in a Pooled Safety Analysis
- Author
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Melhem Solh, Juan Pablo Alderuccio, Brian Hess, John Radford, Matt Lunning, David Ungar, Muneet Burke, Luqiang Wang, and Kirit Ardeshna
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2021
36. ABCL-022: LOTIS-2 Follow-Up Analysis: Updated Results from a Phase 2 Study of Loncastuximab Tesirine (Lonca) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Author
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Juan Pablo Alderuccio, Weiyun Z. Ai, Brian T. Hess, Mehdi Hamadani, Kirit M. Ardeshna, Melhem Solh, Anastasios Stathis, Carmelo Carlo-Stella, John Radford, Jay Feingold, Paolo Caimi, Shui He, Yajuan Qin, Brad S. Kahl, David Ungar, and Pier Luigi Zinzani
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,Anemia ,Phases of clinical research ,Context (language use) ,Hematology ,Neutropenia ,medicine.disease ,Gastroenterology ,Discontinuation ,Oncology ,Refractory ,Internal medicine ,Medicine ,Refractory Diffuse Large B-Cell Lymphoma ,business ,Diffuse large B-cell lymphoma - Abstract
Context Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are ineligible for, or relapse after, salvage chemotherapy/stem cell transplant (SCT) have a poor prognosis. Lonca comprises a humanized anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin. Objective To assess updated efficacy and safety findings from a Phase 2 study evaluating Lonca in patients with R/R DLBCL (LOTIS-2; NCT03589469). Design Multicenter, open-label, single-arm Phase 2 study in adult patients (≥18 years) with pathologically defined R/R DLBCL and ≥2 prior systemic treatments. Intervention Lonca (150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W thereafter). Main Outcomes Measures Primary efficacy endpoint: Overall response rate (ORR), assessed by central review. Secondary efficacy endpoints: Duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Safety analyses: Treatment-emergent adverse events (TEAEs). Follow-up period: Q12W for ≤3 years after end of treatment. Results 145 patients with R/R DLBCL received ≥1 Lonca dose. Median age was 66 years (range 23–94). Patients received a median of 3 prior therapies (range 2–7). At data cut-off (October 26, 2020, ≥12 months since first dose), 2 patients continued treatment. Patients received a mean of 4.6 Lonca cycles (std 4.1; range 1–22). ORR was 48.3% (complete response [CR]: 24.8%; partial response [PR]: 23.4%). Median DoR was 12.6 months for patients with CR or PR (n=70); not reached for patients with CR. Median PFS and OS were 4.9 and 9.5 months, respectively. Post-Lonca treatment, 15 patients received CD19-directed chimeric antigen receptor T-cell therapy with an investigator-assessed ORR of 46.7%, and 11 patients proceeded to SCT as consolidation after Lonca response. Most common (≥25.0%) all-grade TEAEs were increased gamma-glutamyltransferase (41.4%), neutropenia (40.0%), thrombocytopenia (33.1%), fatigue (27.6%), and anemia (26.2%). Grade ≥3 TEAEs occurred in 107 (73.8%) patients. Treatment-related TEAEs leading to treatment discontinuation and dose delays occurred in 26 (17.9%) and 62 (42.8%) patients, respectively. Conclusions After longer follow-up of patients in LOTIS-2, durable responses to Lonca continue to be observed in heavily pre-treated patients with R/R DLBCL. No new safety concerns occurred. Research funding ADC Therapeutics SA.
- Published
- 2021
37. ABCL-396: Incidence, Onset, and Management of Edema and Effusion in Patients Treated with Loncastuximab Tesirine for R/R DLBCL in the LOTIS Clinical Trial Program
- Author
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Juan Pablo Alderuccio, Kirit Ardeshna, Brian Hess, John Radford, Matt Lunning, David Ungar, Muneet Burke, Luqiang Wang, and Melhem Solh
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2021
38. Expression of germinal center cell markers by extranodal marginal zone lymphomas of MALT type within colonized follicles, a diagnostic pitfall with follicular lymphoma
- Author
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Jennifer R. Chapman, Julio Poveda, Izidore S. Lossos, Francisco M. Vega, Juan Pablo Alderuccio, Daniel P. Cassidy, and Yi Zhou
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Follicular lymphoma ,Context (language use) ,Biology ,Stem cell marker ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Follicular phase ,medicine ,Biomarkers, Tumor ,Tumor Microenvironment ,Humans ,Lymphoma, Follicular ,Germinal center ,Hematology ,Lymphoma, B-Cell, Marginal Zone ,Marginal zone ,BCL6 ,medicine.disease ,Germinal Center ,Oncology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,030215 immunology - Abstract
We reviewed 341 consecutive cases of marginal zone lymphoma (MZL) (47) or follicular lymphoma (FL) (294) of which 7 were difficult to distinguish due to perceived coexpression of BCL6 and BCL2 by tumor cells in follicular foci. This stimulated us to develop dual BCL6/BCL2 immunohistochemistry, allowing us to assess coexpression among individual cells. Dual staining confirmed coexpression in 6 of 7 cases, all extranodal MZL (ENMZL) based on overall features and representing 13% of MZL in this series. These findings confirm that MZL cells have plasticity regarding protein expression within the germinal center (GC) microenvironment, an important diagnostic pitfall. Intriguingly, in all MZL expressing BCL6, non-neoplastic GC B cells within colonized follicles showed diminished or absent CD10 expression but preserved BCL6 and high ki67. This finding suggests plasticity of CD10 expression in non-neoplastic GC B cells in the context of colonization by MZL, possibly related to NF-kB dysregulation.
- Published
- 2020
39. Long-term outcomes of frontline
- Author
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Izidore S, Lossos, Isildinha M, Reis, Joseph D, Rosenblatt, and Juan Pablo, Alderuccio
- Subjects
Treatment Outcome ,Antibodies, Monoclonal ,Humans ,Yttrium Radioisotopes ,Lymphoma, B-Cell, Marginal Zone ,Radioimmunotherapy - Published
- 2020
40. Survival analysis in treated plasmablastic lymphoma patients: a population-based study
- Author
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Izidore S. Lossos, Isildinha M. Reis, Juan Pablo Alderuccio, and Jorge A. Florindez
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Population ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Epidemiology ,medicine ,Humans ,Registries ,Stage (cooking) ,education ,Child ,Survival rate ,Survival analysis ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,United States ,Population based study ,Survival Rate ,B symptoms ,030220 oncology & carcinogenesis ,Plasmablastic Lymphoma ,Female ,medicine.symptom ,business ,Plasmablastic lymphoma ,030215 immunology - Abstract
Herein we analyzed survival outcomes in chemotherapy-treated patients with plasmablastic lymphoma (PBL) diagnosed between 2010 to 2016 (n = 248). Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database (April 2019 release based on November 2018 submission). The majority of patients were male (81.9%) and younger than 60 years (71.0%). Oral and gastrointestinal (GI) sites were the most frequent primary extranodal locations (23% and 19.4%, respectively). Oral primary location was inversely associated with presence of B symptoms and advanced Ann-Arbor stage. The 3-year and 5-year overall survival (OS) rates of treated PBL patients were 54% (95% CI: 46.5%-60.8%) and 52.8% (95% CI: 45.2%-59.8%). Three-year conditional survival for 2-year and 3-year survivors were 90.3% and 97.8%, overlapping the survival of a general population matched by age, sex and calendar year. In a multivariable analysis, oral primary location was associated with not only better OS (HR 0.43; 95% CI: 0.21-0.88, P = .021) but also better lymphoma-specific survival (LSS) (SHR 0.36; 95% CI: 0.15-0.86, P = .022); age ≥60 years was associated with shorter LSS (SHR 1.73; 95% CI: 1.02-2.96, P = .043). Seven registries granted access to HIV status (n = 93) where HIV infection was detected in 52.7% of cases. The HIV status did not affect survival outcomes in unadjusted and adjusted analyses. We identified clinical characteristics associated with survival and showed that treated PBL patients may achieve long-term survival.
- Published
- 2020
41. Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers
- Author
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Allandria Straker-Edwards, Catherine Wei, Paolo Caimi, Andreas K. Klein, Michael C. Churnetski, Suchitra Sundaram, Deepa Jagadeesh, Andrew M. Evens, Neil Palmisiano, Catherine Diefenbach, Matthew A. Lunning, Kevin A. David, Agrima Mian, Adam J. Olszewski, Parameswaran Venugopal, Manali Kamdar, Nadia Khan, Albert Ren, Veronika Bachanova, Umar Farooq, Vaishalee P. Kenkre, Craig A. Portell, Nishitha Reddy, Tatyana Feldman, Victor M. Orellana-Noia, Alexey V. Danilov, Gaurav Varma, Jeremy Ramdial, Seema Naik, Yun Kyong Choi, Ayushi Chauhan, Tycel Phillips, Kristie A. Blum, Madelyn Burkart, Andrzej Stadnik, Reem Karmali, Stephen D. Smith, Ryan Vaca, Christopher D'Angelo, Daniel Rector, Brad M. Haverkos, Narendranath Epperla, Amy Sperling, Juan Pablo Alderuccio, Yong Lin, Seth M. Maliske, Stephanie Berg, Izidore S. Lossos, Malvi Savani, Seo-Hyun Kim, Maryam Sarraf Yazdy, Amandeep Godara, David A. Bond, Peter Martin, Adam Zayac, Scott E. Smith, Emma Rabinovich, and Kirsten M Boughan
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Immunology ,Perforation (oil well) ,Kaplan-Meier Estimate ,Biochemistry ,Gastroenterology ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Aged ,Gene Rearrangement ,Performance status ,L-Lactate Dehydrogenase ,business.industry ,Proportional hazards model ,Cancer ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Burkitt Lymphoma ,Progression-Free Survival ,United States ,Lymphoma ,030104 developmental biology ,Treatment Outcome ,Respiratory failure ,Rituximab ,Female ,business ,030215 immunology ,medicine.drug - Abstract
We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.
- Published
- 2020
42. Splenic marginal zone lymphoma: A US population-based survival analysis (1999-2016)
- Author
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Isildinha M. Reis, Juan Pablo Alderuccio, Izidore S. Lossos, and Jorge A. Florindez
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Splenectomy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Splenic marginal zone lymphoma ,Survival analysis ,Chemotherapy ,business.industry ,Hazard ratio ,Population based survival ,Lymphoma, B-Cell, Marginal Zone ,Middle Aged ,medicine.disease ,Survival Analysis ,Lymphoma ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,SEER Program - Abstract
BACKGROUND Splenic marginal zone lymphoma (SMZL) is a rare tumor without a uniform treatment approach. The authors describe a large population-based study evaluating survival outcomes of patients with SMZL according to the treatment received. METHODS From the Surveillance, Epidemiology, and End Results database, patients were selected who had SMZL diagnosed from 1999 to 2016. Observation, splenectomy, chemotherapy, and splenectomy with chemotherapy were the evaluated treatment strategies. Cox and Fine and Gray regression models were used to evaluate overall and SMZL-specific survival, respectively. RESULTS In total, 1671 patients were selected for the analysis. Most patients were aged >60 years (71.3%), White (89.7%), and non-Hispanic (91.7%). Transformation to diffuse large B-cell lymphoma (DLBCL) occurred in 71 patients (4.2%), and the 10-year transformation rate was 8.6% (95% CI, 6.6%-10.9%). In multivariable analysis, shorter SMZL-specific survival was associated with age ≥60 years (subdistribution hazard ratio [SHR], 1.85; 95% CI, 1.40-2.45; P
- Published
- 2020
43. Rapid complete response to blinatumomab as a successful bridge to allogeneic stem cell transplantation in a case of refractory Richter syndrome
- Author
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Jennifer R. Chapman, Juan Pablo Alderuccio, Izidore S. Lossos, Nicholas Mackrides, and Francisco Vega
- Subjects
Cancer Research ,business.industry ,Chronic lymphocytic leukemia ,Hematology ,medicine.disease ,Lymphoma ,Transplantation ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,Bridge (graph theory) ,Oncology ,Refractory ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Blinatumomab ,Stem cell ,business ,030215 immunology ,medicine.drug - Abstract
Richter’s syndrome (RS), also known as Richter’s transformation, is defined as a transformation of chronic lymphocytic leukemia (CLL) to a more aggressive subtype, typically diffuse large B-cell ly...
- Published
- 2018
44. ONGOING PHASE 1B/2 TRIALS OF MOSUNETUZUMAB INVESTIGATING NOVEL TREATMENT REGIMENS FOR PATIENTS WITH B-CELL NON-HODGKIN LYMPHOMA (NHL)
- Author
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V.G. Karur, Adam J. Olszewski, Antonia Kwan, Houston Holmes, B.M. Medeiros, Izidore S. Lossos, Anusha Vallurupalli, Mehdi Hamadani, Julio C. Chavez, Chunze Li, Michael C. Wei, Shen Yin, E. Seymour, Carol O'Hear, Lihua E. Budde, Javier Munoz, Betsy Althaus, Herbert Eradat, Juan Pablo Alderuccio, and S. Babu
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Treatment regimen ,business.industry ,Internal medicine ,medicine ,B-Cell Non-Hodgkin Lymphoma ,Hematology ,General Medicine ,business - Published
- 2019
45. Long-Term Outcome of Conjunctival Extranodal Marginal Zone Lymphoma: A Large Single-Institution Analysis
- Author
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Amrita Desai, Arnold M. Markoe, Derek Isrow, Gregor Rodriguez, Sunil Iyer, Juan Pablo Alderuccio, Eduardo Edelman Saul, Wei Zhao, Isildinha M. Reis, and Izidore S. Lossos
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Marginal zone lymphoma ,Medicine ,Cell Biology ,Hematology ,Single institution ,business ,Biochemistry ,Outcome (game theory) ,Term (time) ,Surgery - Abstract
Background The most common subtype of B-cell lymphomas presenting in the conjunctiva is extranodal marginal zone lymphoma (EMZL), accounting for ~80% of cases. Most patients (pts) present with localized disease, and radiation therapy (RT) is the preferred treatment strategy. We aimed to retrospectively analyze our single-institution experience to provide further insight into the characteristics and long-term outcomes of conjunctival EMZL. Methods We evaluated 72 pts diagnosed with conjunctival EMZL between 01/1995 and 12/2020 at the University of Miami. Pts' characteristics included age, sex, TNM-AJCC ocular lymphoma and Ann Arbor staging systems, MALT-IPI score, treatment (RT, chemotherapy, rituximab), and treatment response (complete response (CR), partial response, stable disease, progression of disease). Primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meier method, and compared using the log rank test and the univariable Cox regression analysis. We also performed a competing risk univariable analysis (UVA) assessing predictors of cumulative incidence of relapse/progression, with death without relapse as a competing risk, using the Fine and Gray regression analysis. Results Among all 72 pts, mean age was 59.9 yrs (7-93) with 38 (52.8%) being >60 yrs old, 46 (63.9%) were female, 56 (77.8%) had unilateral conjunctival disease, localized disease (T1N0M0 and Ann Arbor stage I) was present in 63 (87.5%), 6 (8.3%) had disseminated disease with more than 1 extranodal site involved, and 29 (40.3%) had a MALT-IPI of 1 or 2. After biopsy and surgical removal, 65 (90.2%) received additional treatment, while 6 (8.3%) were followed only, and in one case therapy information was not available . RT was the most common treatment (53 pts [73.6%], with 46 [86.8%] of those treated with ≥ 30 Gy). In two of these patients RT was combined with chemotherapy. Other treated pts received immunochemotherapy (12 [16.7%], including rituximab in 8). Five pts with stage II-IV disease received systemic therapy. CR was achieved in 63 (87.5%) after first line treatment, and no high-grade lymphoma transformation was seen. With a median follow up of 6.67 yrs (0.56-24.13), there were 14 relapses (19.4%). Among 53 pts treated with RT there were 8 relapses (15.1%), only one (1.9%) within the RT field. There were 23 progression events (31.9%, 14 relapses and 9 deaths without documented relapse), and a total of 14 deaths (19.4%). Mean PFS and OS were 6.69 yrs (0.49-20.37, SD 4.95) and 7.81 yrs (0.56-24.13, SD 5.40), respectively. The 10-yr PFS and OS were 68.4% (95%CI 52.8, 79.8%) and 89.4% (95%CI 77.4, 95.2%), respectively. Variables associated with shorter PFS in UVA Cox model were age > 60 yrs (HR=2.93, 95%CI 1.08, 7.95; p=0.035), high MALT-IPI (1-2) (HR=2.42, 95%CI 1.01, 5.78; p=0.048), and use of chemotherapy only (HR=2.73, 95%CI 1.13, 6.56; p=0.025). Variables associated with shorter OS included age >60 yrs (HR=9.07, 95%CI 1.17, 70.26; p=0.035) and high MALT-IPI (HR=6.19, 95%CI 1.35, 28.33; p=0.019). CR after frontline therapy was associated with longer PFS (HR=0.13, 95%CI 0.04, 0.45; p=0.001) but not OS. PFS of MALT-IPI 0 vs 1-2 was significantly longer (p=0.042), with 10-yr PFS 80.9% (95%CI 63.4%, 90.6%) vs 55.6% (95%CI 32.1%, 73.8%). Similarly, longer OS was observed in MALT-IPI 0 pts (p=0.0077; 10-yr OS 95.2% [95%CI 82.2%, 98.8%] vs 80.6% [95%CI 55.6%, 92.4%]) (Figure). A subset UVA Cox analysis of patients with Ann Arbor stage I showed longer PFS associated with CR after frontline therapy (HR 0.15, 95%CI 0.04, 0.58; p=0.006) with no significant association with age >60 yrs, high MALT-IPI or use of chemotherapy. Variables associated with shorter OS were age >60 yrs (HR 8.01, 95%CI 1.00, 63.98; p=0.05) and high MALT-IPI (HR 13.41, 95%CI 1.67, 107.99; p=0.015), similarly to the primary analysis. On univariable Fine and Gray regression models with death without relapse/progression as a competing risk, RT (SHR=0.33, 95%CI 0.12, 0.96; p=0.041) and CR-post frontline therapy (SHR=0.11, 95%CI 0.03, 0.36; p Conclusion Patients with conjunctival EMZL exhibit excellent long-term survival, and RT remains the most effective frontline therapy. MALT-IPI appropriately identifies patients at risk for treatment failure. Figure 1 Figure 1. Disclosures Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member. Lossos: Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; NCI: Research Funding; Stanford University: Patents & Royalties; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment.
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- 2021
46. Clinical Characteristics and Responses of Patients with Relapsed or Refractory High-Grade B-Cell Lymphoma Treated with Loncastuximab Tesirine in the Lotis-2 Clinical Trial
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Carmelo Carlo-Stella, Pier Luigi Zinzani, Juan Pablo Alderuccio, Matthew A. Lunning, Yajuan Qin, Kirit M. Ardeshna, John Radford, Anastasios Stathis, Melhem Solh, Brian T. Hess, Paolo F. Caimi, Weiyun Z. Ai, Brad S. Kahl, Eric H.C. Yu, David Ungar, Mehdi Hamadani, and Turk Kilavuz
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Clinical trial ,medicine.medical_specialty ,Refractory ,business.industry ,Internal medicine ,Immunology ,High grade B-cell lymphoma ,Medicine ,Cell Biology ,Hematology ,business ,Biochemistry ,Gastroenterology - Abstract
Introduction: Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA-approved CD19-directed antibody-drug conjugate (ADC) indicated for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after ≥2 lines of systemic therapy, including patients with high-grade B-cell lymphoma. In the Phase 2 LOTIS-2 trial (NCT03589469), Lonca was evaluated as a single agent in patients with R/R diffuse large B-cell lymphoma (DLBCL) and the overall response rate (ORR) was 48.3% (Caimi PF, et al. Lancet Oncol. 2021; 22:790-800). In an analysis of the 11 patients from the LOTIS-2 clinical trial with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL; data cutoff: April 6, 2020), 45.5% (n=5) achieved an overall response. In this patient subgroup, the median duration of response was 13.37 months, and the median progression-free survival was 9.13 months. The aim of this analysis (data cut off: March 1, 2021) was to further characterize the clinical characteristics and efficacy of Lonca in patients with HGBCL enrolled in the LOTIS-2 clinical trial. Methods: The methodology for the LOTIS-2 trial has been published. Briefly, Lonca (0.15 mg/kg for the first 2 cycles followed by 0.075 mg/kg for subsequent cycles) was administered as a single 30-minute infusion, once every 3 weeks for up to 1 year, until progressive disease or unacceptable toxicity. The primary outcome was ORR defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR), assessed by independent review. Investigator assessment of histopathology according to the 2016 WHO classification was used to define HGBCL. Results: The demographics and disease characteristics of the 11 patients with HGBCL are shown in Table 1. The median age was 74 years; 5 patients (45.5%) were age ≥75 years. The majority of patients received ≥3 prior lines of therapy (n = 8; 72.7%). One patient had a prior stem cell transplant (autologous; 9.1%). Of the 11 patients with HGBCL, the overall response rate was 45.5%, with all 5 patients achieving CR. The median (min, max) time to first CR or PR response was 43.0 (38, 148) days and the median time to first CR response was 79.0 (38, 148) days. All five responding patients (45.5%) had a duration of response ≥1 year; median duration of response has not been reached at the time of data cutoff. Conclusions: Efficacy data from this small subgroup of patients with HGBCL enrolled in the LOTIS-2 clinical trial are consistent with the overall trial population. These results suggest that Lonca is active in the treatment of this high-risk lymphoma subgroup, achieving comparable response rates with other risk groups and with long-term disease control in responding patients. Funding: This study was funded by ADC Therapeutics; medical writing support was provided by CiTRUS Health Group. Figure 1 Figure 1. Disclosures Alderuccio: Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Puma Biotechnology: Other: Family member; ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Forma Therapeutics: Other: Family member. Ai: Kymria, Kite, ADC Therapeutics, BeiGene: Consultancy. Radford: ADC Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Speakers Bureau; BMS: Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Current holder of individual stocks in a privately-held company. Solh: Jazz Pharmaceuticals: Consultancy; BMS: Consultancy; Partner Therapeutics: Research Funding; ADCT Therapeutics: Consultancy, Research Funding. Ardeshna: Gilead, Beigene, Celegene, Novartis and Roche: Honoraria; Norvartis, BMS, Autolus, ADCT, Pharmocyclics and Jansen: Research Funding; Gilead, Beigene, Celegene, Novartis and Roche: Membership on an entity's Board of Directors or advisory committees. Lunning: AbbVie: Consultancy; Novartis: Consultancy; Beigene: Consultancy; ADC Therapeutics: Consultancy; Daiichi-Sankyo: Consultancy; Spectrum: Consultancy; Acrotech: Consultancy; AstraZeneca: Consultancy; Myeloid Therapeutics: Consultancy; Janssen: Consultancy; Verastem: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; Kite, a Gilead Company: Consultancy; Kyowa Kirin: Consultancy; Karyopharm: Consultancy; TG Therapeutics: Consultancy; Morphosys: Consultancy; Legend: Consultancy. Hess: BMS: Speakers Bureau; ADC Therapeutics: Consultancy. Zinzani: EUSAPHARMA: Consultancy, Other, Speakers Bureau; SANDOZ: Other: Advisory board; ROCHE: Other, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; Beigene: Other, Speakers Bureau; Incyte: Other, Speakers Bureau; ADC Therap.: Other; SERVIER: Other: Advisory board, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Stathis: Abbvie and PharmaMar: Other: travel grant; Pfizer, ADC Therapeutics, Bayer, Roche, Merck, Novartis, MEI Therapeutics and Abbvie: Research Funding; Bayer / Eli Lilly: Consultancy. Carlo-Stella: Sanofi: Consultancy, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Janssen Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees. Hamadani: Sanofi, Genzyme, AstraZeneca, BeiGene: Speakers Bureau; Janssen, Incyte, ADC Therapeutics, Omeros, Morphosys, Kite: Consultancy; Takeda, Spectrum Pharmaceuticals and Astellas Pharma: Research Funding. Kahl: AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding; AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy. Ungar: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Kilavuz: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Yu: ADC Therapeutics: Current Employment. Qin: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Caimi: TG Therapeutics: Honoraria; Amgen Therapeutics.: Consultancy; XaTek: Patents & Royalties: Royalties from patents (wife); ADC Theraputics: Consultancy, Research Funding; Seattle Genetics: Consultancy; Verastem: Consultancy; Genentech: Research Funding; Kite Pharmaceuticals: Consultancy.
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- 2021
47. Localized DLBCL of the Tonsil: A U.S. Population-Based Survival Analysis
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Juan Pablo Alderuccio, Izidore S. Lossos, and Jorge A Florindez
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Oncology ,medicine.medical_specialty ,medicine.anatomical_structure ,Internal medicine ,Tonsil ,Immunology ,medicine ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Survival analysis ,U s population - Abstract
INTRODUCTION: The Waldeyer ring represents a common location of diffuse large B-cell lymphoma (DLBCL) arising in the head and neck. Within the Waldeyer ring, tonsils are the most common site. Chemotherapy with or without consolidation with radiotherapy are the most common approaches. However, the benefit of radiotherapy over chemotherapy as a single approach in patients with localized DLBCL remains unclear. In this study we analyzed the survival effect of different treatment modalities along with clinical variables in two cohorts of patients with stage I DLBCL involving either the tonsils or the neck lymph nodes (LN). METHODS: This is a retrospective analysis of patients with stage I DLBCL with primary involvement of the tonsil or neck lymph nodes derived from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2015 with follow up through 2017. We concentrated our analysis on patients with Ann Arbor stage I and treated with chemotherapy and/or radiotherapy. We excluded cases without histologic confirmation, untreated, incomplete survival data or unknown cause of death. The major end-points of this study were overall survival (OS) and lymphoma-specific survival (LSS). Kaplan-Meier and log-rank test were used in the OS analysis with Cox proportional hazard regression model to assess predictors of OS. LSS was evaluated using competing risk analysis. The Fine and Gray subdistribution hazard model was used to assess the effect of demographic and treatment related variables on the risk of lymphoma-specific death. We reported subdistribution hazard ratios (SHR) with corresponding 95% confidence intervals. RESULTS: 1978 (tonsil: 311 and neck LN: 1667) patients with DLBCL met the inclusion criteria. Overall, most patients were ≥ 60 years (n=1130, 57.1%), male (n=1101, 55.7%), white (n=1631, 82.5%), non-Hispanic (n=1775, 89.7%), and treated with chemotherapy (n=935, 47.3%) followed by chemotherapy/radiotherapy (n=929, 47%). Patients Patients with tonsil DLBCL exhibited longer median OS compared to neck LN (16.2 vs. 14.2 years; P=0.033) (Figure 1A). In patients with tonsil DLBCL, consolidation with radiation did not lead to longer median 5-year OS (83.9%, 95%CI 76.7-89% vs 81.8%, 95%CI 74.1-87.4%; P=0.523) or LSS (HR=0.73, 95%CI 0.37-1.42; P=0.350) compared to chemotherapy (Figure 1B and Table 1). Contrary, patients with neck LN demonstrated better OS (5-year OS 82.6%, 95% 79.7-85.1 vs 72.2% 95%CI 68.9-75.2%; P CONCLUSION: Based on our analysis consolidation with radiotherapy does not improve OS or LSS in patients with stage I tonsil DLBCL treated with chemotherapy. Conversely, consolidation with radiation significantly improves survival in patients with localized LN DLBCL. Figure 1 Figure 1. Disclosures Lossos: NCI: Research Funding; Seattle Genetics: Consultancy; Stanford University: Patents & Royalties; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member.
- Published
- 2021
48. DA-EPOCH-R for Adult Burkitt’s Lymphoma: Pros and Cons
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Izidore S. Lossos and Juan Pablo Alderuccio
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Pediatrics ,medicine.medical_specialty ,Oncology (nursing) ,business.industry ,Health Policy ,cons ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Adult Burkitt's lymphoma ,030220 oncology & carcinogenesis ,medicine ,EPOCH (chemotherapy) ,business ,030215 immunology - Published
- 2018
49. Poster: ABCL-362: Incidence, Onset, and Management of Myelosuppression in Patients Treated with loncastuximab Tesirine for R/R DLBCL in a Pooled Safety Analysis
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Melhem Solh, Luqiang Wang, Brian T. Hess, Juan Pablo Alderuccio, Matt Lunning, Kirit M. Ardeshna, John Radford, Muneet Burke, and David Ungar
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Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,Incidence (epidemiology) ,medicine ,In patient ,Hematology ,business - Published
- 2021
50. Poster: ABCL-022: LOTIS-2 Follow-Up Analysis: Updated Results from a Phase 2 Study of Loncastuximab Tesirine (Lonca) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
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Brad S. Kahl, Mehdi Hamadani, Paolo F. Caimi, Carmelo Carlo-Stella, Weiyun Ai, Juan Pablo Alderuccio, Kirit M. Ardeshna, Brian Hess, John Radford, Melhem Solh, Anastasios Stathis, Jay Feingold, David Ungar, Yajuan Qin, Shui He, and Pier Luigi Zinzani
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Cancer Research ,Oncology ,Hematology - Published
- 2021
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