Search

Your search keyword '"William G Blum"' showing total 21 results
Start Over Author "William G Blum"
21 results on '"William G Blum"'

1. BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma

Author

Martin Vogel, Muna Qayed, Shanmuganathan Chandrakasan, Sharmila Raghunandan, Melinda Pauly, William G Blum, Madhav V Dhodapkar, Mohamed Elkhalifa, Benjamin Watkins, Michelle Schoettler, Edwin Horwitz, Suhag Parikh, Kathryn Leung, Elyse Bryson, Laura Deeb, Jonathan L Kaufman, Diana Worthington-White, Adina Alazraki, Jordan M Schecter, Deepu Madduri, Carolyn C Jackson, Enrique Zudaire, Agne Taraseviciute-Morris, Alexander Babich, Tonia Nesheiwat, Nikoletta Lendvai, Lida Pacaud, and Kirsten M Williams

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA). Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207). However, data for the use of BCMA CAR-T for treating PBL are lacking.We report a challenging case of multiple refractory PBL that emerged from B-cell acute lymphoblastic leukemia in an adolescent who failed to respond to an allogeneic hematopoietic cell transplant. The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND)). The patient achieved a complete remission (CR), without recurrent acute graft versus host disease (GVHD), CRS or ICANS after BCMA CAR-T therapy. BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options.

Published
2023
Full Text
View/download PDF

2. Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study

Author

Krzysztof Mrózek, Jessica Kohlschmidt, James S. Blachly, Deedra Nicolet, Andrew J. Carroll, Kellie J. Archer, Alice S. Mims, Karilyn T. Larkin, Shelley Orwick, Christopher C. Oakes, Jonathan E. Kolitz, Bayard L. Powell, William G. Blum, Guido Marcucci, Maria R. Baer, Geoffrey L. Uy, Wendy Stock, John C. Byrd, and Ann-Kathrin Eisfeld

Subjects
Cancer Research, Oncology, Hematology
Abstract

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged CEBPAbZIP mutations or core-binding factor AML, but changed risk assignment of NPM1-mutated/FLT3-ITD-negative patients to intermediate. NPM1-mutated patients with adverse-risk cytogenetic abnormalities were closer prognostically to the intermediate than adverse group. Our analyses both confirm and challenge prognostic significance of some of the newly added markers.

Published
2023

3. Sex-Associated Differences in Frequencies and Outcome Prognostication of Recurrent Molecular Features in Adults with Acute Myeloid Leukemia (AML) (AMLCG, CALGB [Alliance])

Author

Michael P. Ozga, Deedra Nicolet, Krzysztof Mrózek, Selen Yilmaz, Jessica Kohlschmidt, Karilyn T. Larkin, James S. Blachly, Christopher C. Oakes, Jill Buss, Christopher J. Walker, Shelley Orwick, Vindi Jurinovic, Maja Rothenberg-Thurley, Annika Maria Dufour, Stephanie Schneider, Maria Cristina Sauerland, Dennis Görlich, Utz Krug, Wolfgang E. Berdel, Bernhard Josef Woermann, Wolfgang Hiddemann, Jan Braess, Marion Subklewe, Karsten Spiekermann, Andrew J. Carroll, William G. Blum, Bayard L. Powell, Jonathan E. Kolitz, Joseph O. Moore, Robert James Mayer, Richard M. Stone, Geoffrey L. Uy, Wendy Stock, Klaus H. Metzeler, H. Leighton Grimes, John C. Byrd, Nathan Salomonis, Tobias Herold, Alice S. Mims, and Ann-Kathrin Eisfeld

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

4. A Risk-Adapted Study to Assess the Efficacy of Enasidenib and Subsequent Response-Driven Addition of Azacitidine for Newly Diagnosed IDH2-Mutant AML Patients: 3-Year Follow-up

Author

Eytan Stein, Sheng F Cai, Ying Huang, Andrew Dunbar, Maria R. Baer, Wendy Stock, Tibor Kovacsovics, William G. Blum, Gary J. Schiller, Rebecca L. Olin, James M. Foran, Mark R. Litzow, Tara L. Lin, Prapti A. Patel, Matthew C. Foster, Michael M. Boyiadzis, Robert H. Collins, Jordan Chervin, Abigail B. Shoben, Jo-Anne Vergilio, Nyla A. Heerema, Leonard Rosenberg, Timothy Chen, Ashley O. Yocum, Franchesca Druggan, Sonja Marcus, Mona Stefanos, Molly Martycz, Brian J. Druker, Alice S. Mims, Uma Borate, Amy Burd, John C. Byrd, and Ross L. Levine

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

5. A Phase 1b Dose Escalation and Expansion Study of SNDX-5613, Azacitidine (AZA) and Venetoclax (VEN) in Newly Diagnosed, Patients ≥ 60 Years with Untreated NPM1-Mutated/ FLT3-Wild Type AML or KMT2A-Rearranged Acute Myeloid Leukemia (AML)

Author

Joshua F. Zeidner, Matthew C. Foster, Mary Johnson, Ying Huang, Ronan T. Swords, Eytan Stein, James M. Foran, Maria R. Baer, Wendy Stock, Yazan F. Madanat, Tibor Kovacsovics, Rebecca L. Olin, William G. Blum, Gary J. Schiller, Tara L. Lin, Robert L. Redner, Zeina Al-Mansour, Emily K Curran, Nyla A. Heerema, Molly Martycz, Leonard Rosenberg, Sonja Marcus, Ashley O. Yocum, Timothy Chen, Mona Stefanos, Franchesca Druggan, Amy Burd, Ross L. Levine, Brian J. Druker, Uma Borate, John C. Byrd, and Alice S. Mims

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

6. Entospletinib (ENTO) in Combination with Cytarabine (Ara-C) and Daunorubicin (DNR) in Newly Diagnosed (ND) Adult Patients with NPM1-Mutated and FLT3-ITD Wild-Type Acute Myeloid Leukemia (AML) Is Associated with Good Response and Survival: A Phase 2 Sub-Study of the Beat AML Master Trial

Author

Uma Borate, Rui Li, Ying Huang, Ronan T. Swords, Elie Traer, Eytan Stein, James M. Foran, Maria R. Baer, Vu H. Duong, Wendy Stock, Olatoyosi Odenike, Prapti Patel, Robert H. Collins, Yazan F. Madanat, Tibor Kovacsovics, Michael W. Deininger, Catherine Smith, Rebecca L. Olin, Martha L. Arellano, William G. Blum, Gary J. Schiller, Tara L. Lin, Matthew C. Foster, Michael M. Boyiadzis, Robert L. Redner, Zeina Al-Mansour, Emily K Curran, Nyla A. Heerema, Theophilus J Gana, Molly Martycz, Leonard Rosenberg, Sonja Marcus, Ashley O. Yocum, Timothy Chen, Mona Stefanos, Franchesca Druggan, Amy Burd, Ross L. Levine, Brian J. Druker, John C. Byrd, and Alice S. Mims

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

7. Outcome Prediction By the New 2022 European Leukemia Net (ELN) Genetic-Risk Classification for Adult Patients (Pts) with Acute Myeloid Leukemia (AML): An Alliance Study

Author

Krzysztof Mrózek, Jessica Kohlschmidt, James S. Blachly, Deedra Nicolet, Andrew J. Carroll, Kellie J. Archer, Alice S. Mims, Karilyn T. Larkin, Shelley Orwick, Christopher C. Oakes, Jonathan E. Kolitz, Bayard L. Powell, William G. Blum, Guido Marcucci, Maria R. Baer, Geoffrey L. Uy, Wendy Stock, John C. Byrd, and Ann-Kathrin Eisfeld

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

9. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001

Author

Geoffrey L. Uy, Sumithra J. Mandrekar, Kristina Laumann, Guido Marcucci, Weiqiang Zhao, Mark J. Levis, Heidi D. Klepin, Maria R. Baer, Bayard L. Powell, Peter Westervelt, Daniel J. DeAngelo, Wendy Stock, Ben Sanford, William G. Blum, Clara D. Bloomfield, Richard M. Stone, and Richard A. Larson

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort. Fifty-four patients with a median age of 67 years (range, 60.3-82.7 years) were enrolled; 39 were FLT3-ITD patients (71%) and 15 were FLT3-TKD (29%) patients. The observed 1-year OS (95% confidence interval [CI]) was 62% (45%-78%) for the FLT3-ITD patients (meeting the primary end point 62% vs 30% for a historical control group, P < .0001) and 71% (42%-92%) for the FLT3-TKD patients. The median disease-free survival and OS were 12.2 months (95% CI, 5-16.9) and 15.0 months (95% CI, 10.4-20.1), respectively, in the FLT3-ITD group and 9.6 (95% CI, 1.9 to not available [NA]) and 16.2 months (95% CI, 5.0 to NA) for the FLT3-TKD group. This study suggests that the addition of sorafenib to chemotherapy for FLT3-ITD AML is feasible and may improve the survival of older adults with FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT01253070.

Published
2017
Full Text
View/download PDF

10. Supplementary Data from Entospletinib in Combination with Induction Chemotherapy in Previously Untreated Acute Myeloid Leukemia: Response and Predictive Significance of HOXA9 and MEIS1 Expression

Author

William G. Blum, Arati V. Rao, Hubert Serve, Thomas Oellerich, Yang Pan, Jinfeng Liu, Lauren Long, Veerendra Munugalavadla, Mark D. Minden, Danjie Zhang, Howland E. Crosswell, Tara L. Lin, Shelley Orwick, Alice S. Mims, Bhavana Bhatnagar, James S. Blachly, John C. Byrd, and Alison R. Walker

Abstract

Suppl Figures 1-3, Suppl Table 1 Supplemental Figure 1. Study schema. Supplemental Figure 2. Overall survival in patients treated with ENTO + 7+3. OS is censored on the date the patient was last known to be alive (if it was not known the patient had died by the end of study follow-up). Supplemental Figure 3. Heat map showing single patients (each column) by HOXA9 and MEIS1 categorization, cytogenetic or molecular risk and outcomes.

Published
2023

11. Data from Entospletinib in Combination with Induction Chemotherapy in Previously Untreated Acute Myeloid Leukemia: Response and Predictive Significance of HOXA9 and MEIS1 Expression

Author

William G. Blum, Arati V. Rao, Hubert Serve, Thomas Oellerich, Yang Pan, Jinfeng Liu, Lauren Long, Veerendra Munugalavadla, Mark D. Minden, Danjie Zhang, Howland E. Crosswell, Tara L. Lin, Shelley Orwick, Alice S. Mims, Bhavana Bhatnagar, James S. Blachly, John C. Byrd, and Alison R. Walker

Abstract

Purpose:Spleen tyrosine kinase (SYK) signaling is a proposed target in acute myeloid leukemia (AML). Sensitivity to SYK inhibition has been linked to HOXA9 and MEIS1 overexpression in preclinical studies. This trial evaluated the safety and efficacy of entospletinib, a selective inhibitor of SYK, in combination with chemotherapy in untreated AML.Patients and Methods:This was an international multicenter phase Ib/II study, entospletinib dose escalation (standard 3+3 design between 200 and 400 mg twice daily) + 7+3 (cytarabine + daunorubicin) in phase Ib and entospletinib dose expansion (400 mg twice daily) + 7+3 in phase II.Results:Fifty-three patients (n = 12, phase Ib and n = 41, phase II) with previously untreated de novo (n = 39) or secondary (n = 14) AML were enrolled (58% male; median age, 60 years) in this study. The composite complete response with entospletinib + 7+3 was 70%. Patients with baseline HOXA9 and MEIS1 expression higher than the median had improved overall survival compared with patients with below median HOXA9 and MEIS1 expression. Common adverse events were cytopenias, febrile neutropenia, and infection. There were no dose-limiting toxicities. Entospletinib-related skin rash and hyperbilirubinemia were also observed.Conclusions:Entospletinib with intensive chemotherapy was well-tolerated in patients with AML. Improved survival was observed in patients with HOXA9/MEIS1 overexpression, contrasting published data demonstrating poor survival in such patients. A randomized study will be necessary to determine whether entospletinib was a mediator this observation.

Published
2023

12. BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma

Author

Sharmila Raghunandan, Melinda Pauly, William G Blum, Muna Qayed, Madhav V Dhodapkar, Mohamed Elkhalifa, Benjamin Watkins, Michelle Schoettler, Edwin Horwitz, Suhag Parikh, Shanmuganathan Chandrakasan, Kathryn Leung, Elyse Bryson, Laura Deeb, Jonathan L Kaufman, Diana Worthington-White, Adina Alazraki, Jordan M Schecter, Deepu Madduri, Carolyn C Jackson, Enrique Zudaire, Agne Taraseviciute-Morris, Alexander Babich, Tonia Nesheiwat, Martin Vogel, Nikoletta Lendvai, Lida Pacaud, and Kirsten M Williams

Subjects
Pharmacology, Cancer Research, Oncology, Immunology, Molecular Medicine, Immunology and Allergy
Abstract

Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA). Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1),NCT03548207). However, data for the use of BCMA CAR-T for treating PBL are lacking.We report a challenging case of multiple refractory PBL that emerged from B-cell acute lymphoblastic leukemia in an adolescent who failed to respond to an allogeneic hematopoietic cell transplant. The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND)). The patient achieved a complete remission (CR), without recurrent acute graft versus host disease (GVHD), CRS or ICANS after BCMA CAR-T therapy. BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options.

Published
2023

13. Characterization of Survival Outcomes and Clinical and Molecular Modulators in Adult Patients with Core-Binding Factor Acute Myeloid Leukemia (CBF-AML) Treated with Hidac Consolidation: An Alliance Legacy Study

Author

Jonathan Hyak, Deedra Nicolet, Jessica Kohlschmidt, Kellie J. Archer, James S. Blachly, Karilyn T. Larkin, Bayard L. Powell, Jonathan E. Kolitz, Maria R. Baer, William G. Blum, Geoffrey L. Uy, Wendy Stock, Richard M. Stone, John C. Byrd, Krzysztof Mrózek, Ann-Kathrin Eisfeld, and Alice S. Mims

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

15. Entospletinib in Combination with Induction Chemotherapy in Previously Untreated Acute Myeloid Leukemia: Response and Predictive Significance of

Author

Alison R, Walker, John C, Byrd, James S, Blachly, Bhavana, Bhatnagar, Alice S, Mims, Shelley, Orwick, Tara L, Lin, Howland E, Crosswell, Danjie, Zhang, Mark D, Minden, Veerendra, Munugalavadla, Lauren, Long, Jinfeng, Liu, Yang, Pan, Thomas, Oellerich, Hubert, Serve, Arati V, Rao, and William G, Blum

Subjects
Adult, Homeodomain Proteins, Male, Indazoles, Daunorubicin, Cytarabine, Induction Chemotherapy, Middle Aged, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute, Pyrazines, Humans, Syk Kinase, Female, Myeloid Ecotropic Viral Integration Site 1 Protein
Abstract

Spleen tyrosine kinase (SYK) signaling is a proposed target in acute myeloid leukemia (AML). Sensitivity to SYK inhibition has been linked toThis was an international multicenter phase Ib/II study, entospletinib dose escalation (standard 3+3 design between 200 and 400 mg twice daily) + 7+3 (cytarabine + daunorubicin) in phase Ib and entospletinib dose expansion (400 mg twice daily) + 7+3 in phase II.Fifty-three patients (Entospletinib with intensive chemotherapy was well-tolerated in patients with AML. Improved survival was observed in patients with

Published
2020

16. Results from phase 2 registration trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Lead-in completed, expansion stage ongoing

Author

David A. Rizzieri, Christopher Brooks, William G. Blum, Naveen Pemmaraju, Anthony S. Stein, Sumithira Vasu, Madeleine Duvic, Marina Konopleva, Peter R. McDonald, Andrew A. Lane, Eunice S. Wang, Kendra Sweet, Janice Chen, Hagop M. Kantarjian, and Shay Shemesh

Subjects
Oncology, Cancer Research, Pathology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Blastic plasmacytoid dendritic cell neoplasm, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, In patient, Interleukin-3 receptor, Stage (cooking), business, 030215 immunology
Abstract

7006Background: SL-401 is a targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on BPDCN and other hematologic cancers. BPDCN is a rare, aggressive hematologic m...

Published
2016

18. Efficacy and safety of an anti-FLT3 antibody (LY3012218) in patients with relapsed acute myeloid leukemia

Author

Rebecca B. Klisovic, David Sanford, Hagop M. Kantarjian, Gautam Borthakur, William G. Blum, Jorge E. Cortes, Guido Marcucci, William G. Wierda, Farhad Ravandi, Guillermo Garcia-Manero, Susan P. Whitman, and Alison R. Walker

Subjects
Cancer Research, biology, business.industry, medicine.drug_class, Myeloid leukemia, hemic and immune systems, Monoclonal antibody, Preclinical data, fluids and secretions, Oncology, hemic and lymphatic diseases, embryonic structures, Immunology, biology.protein, Medicine, In patient, Antibody, business
Abstract

7059 Background: LY3012218 (IMC-EB10) is a monoclonal antibody that binds FLT3 with high affinity and prevents binding of the FLT3-ligand and downstream signaling. Preclinical data using LY301228 d...

Published
2015

19. Long-term follow-up of patients with acute myelogenous leukemia receiving an autologous telomerase-based dendritic cell vaccine

Author

Kevin Nishimoto, Edward D. Wirth, Robert H. Collins, William G. Blum, John F. DiPersio, Jane S. Lebkowski, Hanna Jean Khoury, and Patrick J. Stiff

Subjects
Cancer Research, Telomerase, Long term follow up, business.industry, cells, medicine.medical_treatment, Immunotherapy, Dendritic cell, medicine.disease, Clinical trial, enzymes and coenzymes (carbohydrates), Myelogenous, Leukemia, Oncology, Dendritic cell vaccine, embryonic structures, Immunology, Cancer research, medicine, biological phenomena, cell phenomena, and immunity, business, neoplasms
Abstract

7007 Background: A phase II clinical trial was conducted in which subjects with AML were administered a telomerase-based dendritic cell immunotherapy (AST-VAC1; hTERT-DCs). The hTERT-DCs were prepa...

Published
2015

21. Autologous transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation: results of CALGB Study 10001 (Alliance)

Author

Meir Wetzler, Dorothy Watson, Wendy Stock, Gregory Koval, Flora A. Mulkey, Eva E. Hoke, John M. McCarty, William G. Blum, Bayard L. Powell, Guido Marcucci, Clara D. Bloomfield, Charles A. Linker, and Richard A. Larson

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Allogeneic stem cell transplantation is the standard approach to Philadelphia chromosome positive acute lymphoblastic leukemia. We hypothesized that imatinib plus sequential chemotherapy will result in significant leukemia cell cytoreduction in patients with Philadelphia chromosome positive acute lymphoblastic leukemia, allowing collection of normal hematopoietic stem cells uncontaminated by residual BCR/ABL1+ lymphoblasts and thus reduce the likelihood of relapse after autologous stem cell transplantation for patients under 60 years of age without sibling donors. We enrolled 58 patients; 19 underwent autologous and 15 underwent allogeneic stem cell transplantation on study. Imatinib plus sequential chemotherapy resulted in reverse-transcriptase polymerase chain reaction-negative stem cells in 9 patients and remained minimally positive in 4 (6 were not evaluable). Overall survival (median 6.0 years vs. not reached) and disease-free survival (median 3.5 vs. 4.1 years) were similar between those who underwent autologous and those who underwent allogeneic stem cell transplantation. We conclude that autologous stem cell transplantation represents a safe and effective alternative for allogeneic stem cell transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia patients without sibling donors (clinicaltrials.gov identifier:00039377).

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results