On November 19, 2024 Bristol Myers Squibb (NYSE: BMY) reported the presentation of more than 90 data disclosures, including 18 oral presentations, across company-sponsored studies, investigator-sponsored studies and collaborations from its hematology and cell therapy research programs at the 66 th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, to be held from December 7 to 10 in San Diego, California (Press release, Bristol-Myers Squibb, NOV 19, 2024, View Source [SID1234648497]). These data underscore the depth and diversity of the company’s approved products and investigational pipeline and spotlight the next wave of innovative treatment approaches with the potential to transform patient outcomes across hematology and other areas of disease.
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"Our data at ASH (Free ASH Whitepaper) reflect our unique ability to address unmet patient needs with our industry-leading cell therapy portfolio and the continued expansion of our work in targeted protein degradation. These advances have been built on decades of specialized research and experience across clinical development and dedication to patient-centric treatment approaches," said Anne Kerber, senior vice president, head of late clinical development, Hematology, Oncology, and Cell Therapy (HOCT), Bristol Myers Squibb. "This meeting provides us with an opportunity to reinforce our commitment to this critical area of research and highlight our current efforts to transform how hematologic diseases are treated."
Key data being presented by Bristol Myers Squibb and its partners at the 2024 ASH (Free ASH Whitepaper) Annual Meeting and Exposition include:
Cell Therapy
Multiple analyses underscoring durable efficacy and well-established safety of the best-in-class profile of Breyanzi (lisocabtagene maraleucel; liso-cel) in large B-cell lymphoma (LBCL), including five-year follow-up overall survival (OS) data from the TRANSCEND NHL-001 trial, new data from the Phase 3 TRANSFORM 2L LBCL study showing deeper and more durable responses with Breyanzi over former standard of care using circulating tumor DNA (ctDNA) as an earlier surrogate of clinical outcome, and compelling real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry
Longer-term results from TRANSCEND FL and TRANSCEND CLL 004 reinforcing Breyanzi ’s best-in-class and best-in-disease profile in relapsed or refractory (R/R) follicular lymphoma (FL), and its durable responses, sustained complete remissions and updated safety profile in patients with R/R chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)
Additional evaluations highlighting efficacy and safety from the Phase 1/2 TRANSCEND CLL 004 trial analyzing Breyanzi in combination with ibrutinib in patients with R/R CLL and SLL
New analysis highlighting global manufacturing capability, reliability and timely delivery for Abecma (idecabtagene vicleucel; ide-cel) in relapsed or refractory multiple myeloma (RRMM)
First OS and progression-free survival results from a Phase 1 study of GPRC5D-directed CAR T cell therapy (BMS-986393/CC-95266) across all dose levels, supporting first-in-class potential in both B-cell maturation antigen (BCMA)-naïve and BCMA-exposed patients with RRMM
Cell therapy data highlighting its potential beyond blood cancers, with updated Phase 1 data for CD19 NEX-T CAR T in severe, refractory autoimmune diseases, for the first time including patients with multiple sclerosis
Anemia
New COMMANDS trial analyses and real-world evidence on long-term benefit of Reblozyl (luspatercept-aamt) for patients with lower-risk myelodysplastic syndromes (MDS) across subgroups, including patients with ring sideroblasts (RS) and low baseline serum erythropoietin (sEPO)
Targeted Protein Degradation
Updated results from Phase 1/2 CC-220-MM-001 trial supporting clinical and pharmacological activity of iberdomide combined with daratumumab and dexamethasone in transplant-ineligible, newly-diagnosed MM patients, including those with high-risk markers
Results from Phase 1/2 CA057-003 trial evaluating an all-oral combination of mezigdomide and novel agents (EZH2, BET and MEK inhibitors), showing promising efficacy and no new safety signals in patients with RRMM
Multiple data sets highlighting the promising clinical profile of golcadomide across LBCL and FL, including new analyses from Phase 1b DLBCL-001 study showing golcadomide plus R-CHOP has high minimal residual disease (MRD) negativity in high-risk 1L LBCL, and longer follow-up from the Phase 1/2 NHL-001 study demonstrating the potential of golcadomide in combination with rituximab for R/R FL and R/R LBCL
Preclinical analysis evaluating development of fetal hemoglobin (HbF)-activating CELMoD agent BMS-986470 for the treatment of sickle cell disease
Multiple preclinical analyses evaluating potential first-in-class CELMoD agent BMS-986397 targeting casein kinase 1α (CK1α) in acute myeloid leukemia and high-risk MDS harboring functional TP53
Preclinical results for potential first-in-class ligand-directed degrader of BCL6 BMS-986458 demonstrating anti-tumor efficacy in B-cell non-Hodgkin lymphoma (NHL)
Additional information about BMS’ presence at the meeting can be found on the ASH (Free ASH Whitepaper) website.
Selected BMS studies at the 2024 ASH (Free ASH Whitepaper) Annual Meeting and Exposition include:
Abstract Title
Author
Presentation Type/#
Session Title
Session Date/Time (PST)
Autoimmune Disease
Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of BMS-986353 (CC-97540), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy Manufactured Using a Next-Generation Process, for Severe, Refractory Autoimmune Diseases: Updated Data from Ongoing Phase 1, Multicenter, Open-Label Studies
Fabian Müller
Poster Presentation #2088
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
Acute Myeloid Leukemia (AML)
Synergistic Activity of BMS-986397, a First-in-Class α Cereblon (CRBN) E3 Ligase Modulator (CELMoD) Targeting Casein Kinase 1α (CK1α), in Combination with Venetoclax and/or Azacitidine in Preclinical Models of Acute Myeloid Leukemia (AML)
Carmen Jimenez
Poster Presentation #1395
Session: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
Beta Thalassemia
Improvement of Iron Overload Parameters in Patients with Transfusion-Dependent β-Thalassemia Treated with Luspatercept: Data from the Phase 3b Long-Term Rollover Study Following the BELIEVE Trial
John Porter
Poster Presentation #2475
Session: 112. Thalassemia and Globin Gene Regulation: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Luspatercept Improves Fatigue-Related Quality of Life through 5 Years of Treatment in Non-Transfusion Dependent Beta-Thalassemia
Khaled Musallam
Poster Presentation #3857
Session: 112. Thalassemia and Globin Gene Regulation: Poster III
Monday, December 9, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Lymphoma
Circulating Tumor DNA (ctDNA) As an Early Outcome Predictor in Patients (pts) with Second-Line (2L) Large B-Cell Lymphoma (LBCL) after Lisocabtagene Maraleucel (liso-cel) Versus Standard of Care (SOC) Treatment (tx) from the Phase 3, Randomized TRANSFORM Study
Ash Alizadeh
Oral Presentation #72
Session: 628. Aggressive Lymphomas: Cellular Therapies: Novel Strategies for Cell Therapies in Aggressive Lymphomas
Saturday, December 7, 2024: 10:45 AM (1:45 PM ET)
Real-World (RW) Outcomes of Lisocabtagene Maraleucel (liso-cel) As Second-Line (2L) Therapy in Patients (pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): First Results from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry
Maria Silvina Odstrcil Bobillo
Oral Presentation #470
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: CARs, Bispecifics, and ADCs: Progress and Challenges in Aggressive B Cell Lymphoma
Sunday, December 8, 2024: 9:45 AM (12:45 PM ET)
Real-World (RW) Outcomes of Lisocabtagene Maraleucel (liso-cel) in Patients (pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) and Secondary Central Nervous System (sCNS) Involvement from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry
Sairah Ahmed
Oral Presentation #472
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: CARs, Bispecifics, and ADCs: Progress and Challenges in Aggressive B Cell Lymphoma
Sunday, December 8, 2024: 10:15 AM (1:15 PM ET)
Golcadomide (GOLCA) Plus R-CHOP Has High Minimal Residual Disease (MRD) Negativity across High-Risk, Untreated Aggressive B-Cell Lymphoma (a-BCL)
Arnaud Amzallag
Oral Presentation #579
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: New R-CHOP Combinations for Treatment Naïve DLBCL
Sunday, December 8, 2024: 12:30 PM (3:30 PM ET)
Golcadomide (GOLCA) ± Rituximab (RTX) Demonstrates Durable Efficacy and Is Well Tolerated in Patients (pts) with Relapsed/Refractory Follicular Lymphoma (R/R FL): Updated Results from the Phase 1/2 CC-99282-NHL-001 Study
Julio C. Chavez
Poster Presentation #3018
Session: 623. Mantle Cell, Follicular, Waldenströms, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Five-Year Survival of Patients (pts) from Transcend NHL 001 (TRANSCEND) Supports Curative Potential of Lisocabtagene Maraleucel (liso-cel) in Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Jeremy Abramson
Poster Presentation #3125
Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Matching-Adjusted Indirect Comparison (MAIC) of Lisocabtagene Maraleucel (liso-cel) Versus Axicabtagene Ciloleucel (axi-cel) for Second-Line (2L) Treatment of Patients (pts) with Refractory/Early Relapsed (R/R) Large B-Cell Lymphoma (LBCL): Update with 34 Months of Liso-Cel Follow-up
Jeremy Abramson
Poster Presentation #3130
Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Degradation of Ikaros Induces Neutropenia through Altered Transcriptional Programming across Multiple Stages of Neutrophil Development and Maturation
Ajit Dhadve
Poster Presentation #2523
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Matching-Adjusted Indirect Comparison (MAIC) of Efficacy and Safety Outcomes for Lisocabtagene Maraleucel (liso-cel) Versus Axicabtagene Ciloleucel (axi-cel) and Tisagenlecleucel (tisa-cel) for the Treatment of Third-Line or Later (3L+) Relapsed or Refractory (R/R) Follicular Lymphoma (FL)
Alexander P. Boardman
Poster Presentation #3028
Session: 623. Mantle Cell, Follicular, Waldenström, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Longer Follow-up of Golcadomide (GOLCA), a Cereblon E3 Ligase Modulator (CELMoD) Agent ± Rituximab (RTX), in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Jean-Marie Michot
Oral Presentation #869
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Novel Monotherapies or Novel Disease Indications
Monday, December 9, 2024: 3:45 PM (6:45 PM ET)
Lisocabtagene Maraleucel (liso-cel) Combined with Ibrutinib (ibr) for Patients (pts) with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Primary Results from the Open-Label, Phase 1/2 Transcend CLL 004 Study
William Wierda
Oral Presentation #887
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Treating Refractory Disease-Novel Agents and Quality-of-Life
Monday, December 9, 2024: 3:45 PM (6:45 PM ET)
Deciphering the Mechanism of Action of the Novel CELMoD, Golcadomide, during Germinal Center B Cell Immune Response and in a Preclinical Mouse Model of Follicular Lymphoma
Caroline Huber
Oral Presentation #955
Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma
Monday, December 9, 2024: 4:30 PM (7:30 PM ET)
BMS-986458 a Potential First-in-Class, Highly Selective, Potent and Well Tolerated BCL6 Ligand Directed Degrader (LDD) Demonstrates Multi-Modal Anti-Tumor Efficacy for the Treatment of B-Cell Non-Hodgkin’s Lymphoma
Lynda Groocock
Oral Presentation #957
Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma
Monday, December 9, 2024: 5:00 PM (8:00 PM ET)
Lisocabtagene Maraleucel (liso-cel) in Patients (pts) with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Updated Follow-up of Transcend CLL 004
Tanya Siddiqi
Poster Presentation #4633
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III
Monday, December 9, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Lisocabtagene Maraleucel (liso-cel) in Patients (pts) with Relapsed or Refractory (R/R) Follicular Lymphoma (FL): Transcend FL 2-Year Follow-up
Loretta J. Nastoupil
Poster Presentation #4387
Session: 623. Mantle Cell, Follicular, Waldenström, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Monday, December 9, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Multiple Myeloma
Iberdomide, Daratumumab, and Dexamethasone Shows Deep Antimyeloma Activity across Molecular Patient Subsets with Transplant-Ineligible Newly Diagnosed Multiple Myeloma from the CC-220-MM-001 Trial
Michael Amatangelo
Poster Presentation #1973
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
BMS-986393, a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted CAR T Cell Therapy, in Patients (pts) with
Relapsed/Refractory (RR) Multiple Myeloma (MM) and 1–3 Prior Regimens: Updated Phase 1 Safety and Efficacy Results
Susan Bal
Poster Presentation #2069
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
Mezigdomide (MEZI) in Novel-Novel Combinations for Relapsed or Refractory Multiple Myeloma (RRMM): Preliminary Results from the CA057-003 Trial
Luciano Costa
Oral Presentation #677
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Optimizing Therapy in Newly Diagnosed Myeloma and Beyond
Sunday, December 8, 2024: 5:30 PM (8:30 PM ET)
Biomarker Analyses of the CC-92480-MM-001 Trial to Guide Combinatorial Strategies for Mezigdomide
Tracy Chow
Poster Presentation #3261
Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Idecabtagene Vicleucel (Ide-cel) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) with an Inadequate Response to Front-Line Autologous Stem Cell Transplantation (ASCT): KarMMa-2 Cohort 2c Extended Follow-up
Barry Paul
Poster Presentation #3388
Session: 655. Multiple Myeloma: Cellular Therapies: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Global Manufacturing Experience with Idecabtagene Vicleucel in Patients with Relapsed and Refractory Multiple Myeloma
Surbhi Sidana
Poster Presentation #3476
Session: 711. Cell Collection and Manufacturing of HSPCs, CAR-T Cells, and Other Cellular Therapy Products: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Cross-Cohort Correlative Analysis of Clinically High-Risk Patients (pts) Treated with Idecabtagene Vicleucel (ide-cel) in KarMMa-2: Association between Progression-Free Survival (PFS) and Tumor Burden and Immune Status at Apheresis
Maria Chaudhry
Poster
Presentation
#3382
Session: 655. Multiple Myeloma: Cellular Therapies: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Efficacy and Safety with Extended Follow-up in a Phase 1 Study of BMS-986393, a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted CAR T Cell Therapy, in Patients (pts) with Heavily Pretreated Relapsed/Refractory (R/R) Multiple Myeloma
Susan Bal
Oral Presentation #922
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Emerging Targeting Approaches of Cell Therapies for Hematologic Malignancies
Monday, December 9, 2024: 3:30 PM (6:30 PM ET)
Mezigdomide (MEZI) Plus Dexamethasone (DEX) and Bortezomib (BORT) or Carfilzomib (CFZ) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results From the CC-92480-MM-002 Trial
Irwindeep Sandhu
Oral Presentation #1025
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Into the Future: New Drugs and Combinations in Multiple Myeloma
Monday, December 9, 2024: 5:30 PM (8:30 PM ET)
Myelodysplastic Syndromes
The Burden of Transfusion Dependence on Caregivers of Patients with Lower-Risk Myelodysplastic Syndromes in North America and Europe
Maria Diez-Campelo
Oral Presentation #118
Session: 908. Outcomes Research: Myeloid Malignancies: Identifying Problems and Providing Solutions to Delivering Myeloid Malignancy Care
Saturday, December 7, 2024: 10:15 AM (1:15 PM ET)
Long-Term Response Analysis of Transfusion Independence in Erythropoiesis Stimulating Agent-Naive Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes Treated with Luspatercept Vs Epoetin Alfa in the COMMANDS Trial
Guillermo Garcia-Manero
Oral Presentation #350
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Defining and Treating Low Risk MDS
Saturday, December 7, 2024: 4:15 PM (7:15 PM ET)
Clinical Benefits of Achieving Hemoglobin (Hb) Levels ≥ 10 g/dL in Transfusion-Dependent (TD) Erythropoiesis-Stimulating Agent (ESA)-Naive Patients (Pts) with Lower-Risk (LR) Myelodysplastic Syndromes (MDS) Treated with Luspatercept in the COMMANDS Trial
Valeria Santini
Poster Presentation #1818
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
Changes in Red Blood Cell Transfusion Burden with Luspatercept Versus Epoetin Alfa in Patients with Lower-Risk Myelodysplastic Syndromes in the Phase 3, Open-Label, Randomized, Controlled COMMANDS Trial
Guillermo Garcia-Manero
Poster Presentation #1832
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
Real-World Treatment Patterns and Outcomes with Oral Azacitidine Maintenance Therapy in Patients with Acute Myeloid Leukemia
Pramila Krishnamurthy
Poster Presentation #2425
Session: 908. Outcomes Research: Myeloid Malignancies: Poster I
Saturday, December 7, 2024: 5:30 PM-7:30 PM (8:30 PM-10:30 PM ET)
Health-Related Quality of Life of Luspatercept Versus Epoetin Alfa in Red Blood Cell Transfusion-Dependent Lower-Risk Myelodysplastic Syndromes: Results from the Final Datacut of the Phase 3 COMMANDS Study
Esther N. Oliva
Poster Presentation #3216
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Impact of Luspatercept on Healthcare Resource Use (HCRU) Among Patients with Lower-Risk, Myelodysplastic Syndromes (LR-MDS): A Medical Record Review in Canada, Germany, and Spain
Maria Diez-Campelo
Poster Presentation #5055
Session: 903. Health Services and Quality Improvement: Myeloid Malignancies: Poster III
Monday, December 9, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
BMS-986397, a First-in-Class Molecular Glue Degrader of Casein Kinase 1α (CK1α) for the Treatment of Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS) Harboring Functional TP53
Carmen Jiminez
Poster Presentation #4142
Session: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III
Monday, December 9, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Myelofibrosis
Efficacy and Safety of Fedratinib in Patients with Myelofibrosis and Low Baseline Platelet Counts in the Phase 3 Randomized
FREEDOM2 Trial
Haifa Kathrin Al-Ali
Oral Presentation #482
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: JAK Inhibitors in MPDs, Novel Insights and Next-Gen Agents
Sunday, December 8, 2024: 9:45 AM (12:45 PM ET)
Burden and Clinical Outcomes in Patients (pts) with Myelofibrosis (MF) and Anemia Treated with Ruxolitinib (RUX): Data from the Veterans Affairs Corporate Data Warehouse (VACDW)
John O. Mascarenhas
Poster Presentation #3807
Session: 908. Outcomes Research: Myeloid Malignancies: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
Sickle Cell Disease
Development of a ZBTB7A and Wiz Dual Degrading, HbF-Activating CELMoD for the Treatment of Sickle Cell Disease
Emily Rychak
Oral Presentation #169
Session: 113. Sickle Cell Disease, Sickle Cell Trait, and Other Hemoglobinopathies, Excluding Thalassemias: Basic and Translational: Identification of New Molecular Targets to Modulate Sickle Cell Disease
Saturday, December 7, 2024: 2:00 PM (5:00 PM ET)
Rap-536, a Murine Luspatercept Analog Ameliorates Anemia and Vaso-Occlusion in Experimental Model of Sickle Cell Disease
Thiago T. Maciel
Oral Presentation #621
Session: 113. Sickle Cell Disease, Sickle Cell Trait, and Other Hemoglobinopathies, Excluding Thalassemias: Basic and Translational: Attenuating Sickle Cell Disease Complications: Lessons from Pre-clinical Models
Sunday, December 8, 2024: 5:00 PM (8:00 PM ET)
Thrombosis and Anticoagulation
Reversal of The Anticoagulant Effect of Milvexian by 4-Factor PCC and rFVIIa in Healthy Participants*
Victor Dishy
Poster Presentation #2628
Session: 332. Thrombosis and Anticoagulation: Clinical and Epidemiological: Poster II
Sunday, December 8, 2024: 6:00 PM-8:00 PM (9:00 PM-11:00 PM ET)
*Sponsored by the Bristol Myers Squibb-Johnson & Johnson Collaboration
Reblozyl is being developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021.
Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio.
About Milvexian*
Milvexian is an investigational oral, highly selective Factor XIa (FXIa) inhibitor, part of a new class of anticoagulants in development aimed at preventing harmful clotting that restricts blood flow (thrombosis) while preserving the normal clotting process (hemostasis). As a result, milvexian could potentially reduce major cardiovascular events due to harmful clotting without significantly increasing the risk of bleeding. It is currently being studied in the Phase 3 Librexia program, the most comprehensive FXIa clinical development program to date, for the prevention and treatment of major thrombotic conditions.
*Milvexian is an investigational agent and has not been approved for use in any country, for any indication.
BREYANZI U.S. INDICATIONS
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of Use : BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.
adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.
Important Safety Information
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. In clinical trials of BREYANZI, which enrolled a total of 702 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 54% of patients, including ≥ Grade 3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% of patients with a median duration of 5 days (range: 1 to 37 days). One patient had fatal CRS and 5 patients had ongoing CRS at the time of death. The most common manifestations of CRS (≥10%) were fever, hypotension, tachycardia, chills, hypoxia, and headache.
Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.
In clinical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 31% of patients, including ≥ Grade 3 cases in 10% of patients. The median time to onset of neurotoxicity was 8 days (range: 1 to 63 days). Neurologic toxicities resolved in 88% of patients with a median duration of 7 days (range: 1 to 119 days). Of patients developing neurotoxicity, 82% also developed CRS.
The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.
CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Further information is available at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-866-340-7332.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).
Serious Infections
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In clinical trials of BREYANZI, infections of any grade occurred in 34% of patients, with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 3.7%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient who received 4 prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after treatment with BREYANZI. One patient who received 3 prior lines of therapy developed a fatal case of cryptococcal meningoencephalitis 35 days after treatment with BREYANZI.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.
Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections.
Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. In clinical trials of BREYANZI, 35 of 38 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.
Prolonged Cytopenias
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. In clinical trials of BREYANZI, Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 35% of patients, and included thrombocytopenia in 25%, neutropenia in 22%, and anemia in 6% of patients. Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In clinical trials of BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 10% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 30% of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.
Secondary Malignancies
Patients treated with BREYANZI may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.
Effects on Ability to Drive and Use Machines
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Three of 89 (3%) safety evaluable patients with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the 3 patients developed IEC-HS in the setting of ongoing CRS and 1 in the setting of ongoing neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines.
Adverse Reactions
The most common adverse reaction(s) (incidence ≥30%) in:
LBCL are fever, cytokine release syndrome, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.
CLL/SLL are cytokine release syndrome, encephalopathy, fatigue, musculoskeletal pain, nausea, edema, and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease.
FL is cytokine release syndrome. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, and white blood cell decrease.
MCL are cytokine release syndrome, fatigue, musculoskeletal pain, and encephalopathy. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, and platelet count decrease.
Please see full Prescribing Information , including Boxed WARNINGS and Medication Guide .
Abecma U.S. Indication
ABECMA (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA and SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA.
ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS.
Warnings and Precautions:
Early Death:
In KarMMa-3, a randomized (2:1), controlled trial, a higher proportion of patients experienced death within 9 months after randomization in the ABECMA arm (45/254; 18%) compared to the standard regimens arm (15/132; 11%). Early deaths occurred in 8% (20/254) and 0% prior to ABECMA infusion and standard regimen administration, respectively, and 10% (25/254) and 11% (15/132) after ABECMA infusion and standard regimen administration, respectively. Out of the 20 deaths that occurred prior to ABECMA infusion, 15 occurred from disease progression, 3 occurred from adverse events and 2 occurred from unknown causes. Out of the 25 deaths that occurred after ABECMA infusion, 10 occurred from disease progression, 11 occurred from adverse events, and 4 occurred from unknown causes.
Cytokine Release Syndrome (CRS):
CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. Among patients receiving ABECMA for relapsed refractory multiple myeloma in the KarMMa and KarMMa-3 studies (N=349), CRS occurred in 89% (310/349), including ≥ Grade 3 CRS (Lee grading system) in 7% (23/349) of patients and Grade 5 CRS in 0.9% (3/349) of patients. The median time-to-onset of CRS, any grade, was 1 day (range: 1 to 27 days), and the median duration of CRS was 5 days (range: 1 to 63 days). In the pooled studies, the rate of ≥Grade 3 CRS was 10% (7/71) for patients treated in dose range of 460 to 510 x 106 CAR-positive T cells and 5.4% (13/241) for patients treated in dose range of 300 to 460 x 106 CAR-positive T cells.
The most common manifestations of CRS (greater than or equal to 10%) included pyrexia (87%), hypotension (30%), tachycardia (26%), chills (19%), hypoxia (16%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, ARDS, atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, coagulopathy, renal failure, multiple organ dysfunction syndrome and HLH/MAS.
Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.
Of the 349 patients who received ABECMA in clinical trials, 226 (65%) patients received tocilizumab; 39% (135/349) received a single dose, while 26% (91/349) received more than 1 dose of tocilizumab. Overall, 24% (82/349) of patients received at least 1 dose of corticosteroids for treatment of CRS. Almost all patients who received corticosteroids for CRS also received tocilizumab. For patients treated in dose range of 460 to 510 x 106 CAR-positive T cells, 76% (54/71) of patients received tocilizumab and 35% (25/71) received at least 1 dose of corticosteroids for treatment of CRS. For patients treated in dose range of 300 to 460 x 106 CAR-positive T cells, 63% (152/241) of patients received tocilizumab and 20% (49/241) received at least 1 dose of corticosteroid for treatment of CRS.
Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of CRS and monitor patients for signs or symptoms of CRS for at least 4 weeks after ABECMA infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.
Neurologic Toxicities:
Neurologic toxicities, including immune-effector cell-associated neurotoxicity (ICANS), which may be severe or life-threatening, occurred concurrently with CRS, after CRS resolution, or in the absence of CRS following treatment with ABECMA.
In patients receiving ABECMA in the KarMMa and KarMMa-3 studies, CAR T cell-associated neurotoxicity occurred in 40% (139/349), including Grade 3 in 4% (14/349) and Grade 4 in 0.6% (2/349) of patients. The median time to onset of neurotoxicity was 2 days (range: 1 to 148 days). The median duration of CAR T cell-associated neurotoxicity was 8 days (range: 1 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. CAR T cell-associated neurotoxicity resolved in 123 of 139 (88%) patients and median time to resolution was 5 days (range: 1 to 245 days).One-hundred and thirty four out of 349 (38%) patients with neurotoxicity had CRS. The onset of neurotoxicity during CRS was observed in 93 patients, before the onset of CRS in 12 patients, and after the CRS event in 29 patients. The rate of Grade 3 or 4 CAR T cell-associated neurotoxicity was 5.6% (4/71) and 3.7% (9/241) for patients treated in dose range of 460 to 510 x 106 CAR-positive T cells and 300 to 460 x 106 CAR-positive T cells, respectively. The most frequent (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (21%), headache (15%), dizziness (8%), delirium (6%), and tremor (6%).
At the safety update for KarMMa-3 study, one patient developed fatal neurotoxicity 43 days after ABECMA. In KarMMa, one patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff.
Cerebral edema has been associated with ABECMA in a patient in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have occurred after treatment with ABECMA in another study in multiple myeloma.
Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of neurologic toxicities and monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after ABECMA infusion and treat promptly. Rule out other causes of neurologic symptoms. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Counsel patients to seek immediate medical attention should signs or symptoms occur at any time.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS):
In patients receiving ABECMA in the KarMMa and KarMMa-3 studies, HLH/MAS occurred in 2.9% (10/349) of patients. All events of HLH/MAS had onset within 10 days of receiving ABECMA, with a median onset of 6.5 days (range: 4 to 10 days) and occurred in the setting of ongoing or worsening CRS. Five patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction and cytopenia.
In KarMMa-3, one patient had Grade 5, two patients had Grade 4 and two patients had Grade 3 HLH/MAS. The patient with Grade 5 HLH/MAS also had Grade 5 candida sepsis and Grade 5 CRS. In another patient who died due to stroke, the Grade 4 HLH/MAS had resolved prior to death. Two cases of Grade 3 and one case of Grade 4 HLH/MAS had resolved.
In KarMMa, one patient treated in the 300 x 106 CAR-positive T cells dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved.
HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional guidelines.
ABECMA REMS:
Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at www.AbecmaREMS.com or contact Bristol Myers Squibb at 1-866-340-7332.
Hypersensitivity Reactions:
Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA.
Infections:
ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion.
In all patients receiving ABECMA in the KarMMa and KarMMa-3 studies, infections (all grades) occurred in 61% of patients. Grade 3 or 4 infections occurred in 21% of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 7%, bacterial infections in 4.3%, and fungal infections in 1.4% of patients. Overall, 15 patients had Grade 5 infections (4.3%); 8 patients (2.3%) with infections of pathogen unspecified, 3 patients (0.9%) with fungal infections, 3 patients (0.9%) with viral infections, and 1 patient (0.3%) with bacterial infection.
Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to standard institutional guidelines.
Febrile neutropenia was observed in 38% (133/349) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.
Viral Reactivation: Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.
Prolonged Cytopenias:
In patients receiving ABECMA in the KarMMa and KarMMa-3 studies, 40% of patients (139/349) experienced prolonged Grade 3 or 4 neutropenia and 42% (145/349) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. In 89% (123/139) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 76% (110/145) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 1.9 months. Five patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. The rate of Grade 3 or 4 thrombocytopenia was 62% (44/71) and 56% (135/241) for patients treated in dose range of 460 to 510 x 106 CAR-positive T cells and 300 to 460 x 106 CAR-positive T cells, respectively.
Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to local institutional guidelines.
Hypogammaglobulinemia:
In all patients receiving ABECMA in the KarMMa and KarMMa-3 studies, hypogammaglobulinemia was reported as an adverse event in 13% (46/349) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 37% (130/349) of patients treated with ABECMA.
Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion occurred in 45% (158/349) of patients treated with ABECMA. Forty-one percent of patients received intravenous immunoglobulin (IVIG) post-ABECMA for serum IgG <400 mg/dL.
Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage appropriately per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.
Use of Live Vaccines: The safety of immunization with live viral vaccines during or after ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA.
Secondary Malignancies:
Patients treated with ABECMA may develop secondary malignancies. In KarMMa-3, myeloid neoplasms (four cases of myelodysplastic syndrome and one case of acute myeloid leukemia) occurred in 2.2% (5/222) of patients following treatment with ABECMA compared to none in the standard regimens arm at the time of the safety update. The median time to onset of myeloid neoplasm from ide-cel infusion was 338 days (Range: 277 to 794 days). Three of these five patients have died following the development of myeloid neoplasm. One out of the five cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.
Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy.
Effects on Ability to Drive and Operate Machinery:
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.
Adverse Reactions:
The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) include pyrexia, CRS, hypogammaglobulinemia, infections – pathogen unspecified, musculoskeletal pain, fatigue, febrile neutropenia, hypotension, tachycardia, diarrhea, nausea, headache, chills, upper respiratory tract infection, encephalopathy, edema, dyspnea and viral infections.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Reblozyl U.S. Indication
REBLOZYL is indicated in the U.S. for the treatment of:
anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.
anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndrome with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. In the U.S., REBLOZYL is not indicated for use in patients with non-transfusion-dependent beta thalassemia.
U.S. Important Safety Information:
WARNINGS AND PRECAUTIONS
Thrombosis/Thromboembolism
In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.
Hypertension
Hypertension was reported in 11.4% (63/554) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 2% to 9.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In ESA-refractory or -intolerant adult patients with MDS with normal baseline blood pressure, 26 (30%) patients developed SBP ≥130 mm Hg and 23 (16%) patients developed DBP ≥80 mm Hg. In ESA-naïve adult patients with MDS with normal baseline blood pressure, 23 (36%) patients developed SBP ≥140 mm Hg and 11 (6%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.
Extramedullary Hematopoietic (EMH) Masses
In adult patients with transfusion-dependent beta thalassemia, EMH masses were observed in 3.2% of REBLOZYL-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and REBLOZYL long-term follow-up study).
In a study of adult patients with non-transfusion-dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of REBLOZYL-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. REBLOZYL is not indicated for use in patients with non-transfusion-dependent beta thalassemia.
Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with REBLOZYL in case of serious complications due to EMH masses. Avoid use of REBLOZYL in patients requiring treatment to control the growth of EMH masses.
Embryo-Fetal Toxicity
REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.
ADVERSE REACTIONS
Beta-Thalassemia
Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML).
Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).
ESA-naïve adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included hypertension and dyspnea.
The most common (≥10%) all-grade adverse reactions included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.
ESA-refractory or -intolerant adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients.
The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection.
LACTATION
It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.
DRUG ABUSE POTENTIAL
Abuse: Abuse of REBLOZYL may be seen in athletes for the effects on erythropoiesis. Misuse of drugs that increase erythropoiesis, such as REBLOZYL, by healthy persons may lead to polycythemia, which may be associated with life-threatening cardiovascular complications.
Please see accompanying U.S. Full Prescribing Information for REBLOZYL.
Bristol Myers Squibb: Unlocking the Full Potential of Cell Therapy
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