New data from our multiple myeloma portfolio across targets and molecular approaches show significant progress toward our goal of transforming the treatment paradigm and improving outcomes for patients
Multiple first disclosures including preliminary Phase 1 data for subcutaneous administration of bispecific T cell engager alnuctamab in heavily pretreated multiple myeloma, preliminary Phase 1 results for GPRC5D CAR T in relapsed/refractory multiple myeloma and first results from the Phase 2 KarMMa-2 trial evaluating Abecma in high-risk multiple myeloma
New data for CD19-directed CAR T cell therapy Breyanzi, including longer-term follow up from pivotal Phase 3 TRANSFORM study in second-line relapsed or refractory large B-cell lymphoma
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced the presentation of research across its hematology portfolio at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, which will take place in New Orleans, Louisiana, and virtually, from December 10 to 13, 2022. Data from more than 100 company-sponsored studies will be featured, including 34 oral presentations, highlighting the range of modalities, targets and research platforms the company is advancing and showcasing our commitment to scientific progress across hematologic diseases.
“Our presence at ASH underscores the transformational potential of our diverse pipeline, poised to deliver the next wave of advances in hematology,” said Samit Hirawat, M.D., executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb. “These exciting data, spanning a variety of modalities and targets, demonstrate significant progress toward our goals of improving long-term outcomes across patient populations and finding solutions in important areas of remaining need.”
Key data being presented by Bristol Myers Squibb and its partners at the 2022 ASH Annual Meeting and Exposition include:
Cell Therapy
Hematology
Early Pipeline
To learn more about our science and commitment in hematology, check out the BMS at ASH 2022 content hub. You can find additional information about BMS’ presence at the meeting on the ASH website.
Selected Bristol Myers Squibb studies at the 64th ASH Annual Meeting and Exposition include:
Abstract Title | Author | Presentation Type/# | Session Title | Session Date/Time (CST) |
Beta Thalassemia | ||||
Erythroid Response in Patients with Non-Transfusion-Dependent ß-Thalassemia Treated with Luspatercept: Long-Term Data from the BEYOND Trial | Ali Taher | 112. Thalassemia and Globin Gene Regulation: Poster III | Monday, December 12, 6:00 – 8:00 PM | |
Lymphoma | ||||
Five-Year Results From the Phase 3 Randomized Study AUGMENT: Lenalidomide Plus Rituximab (R2) vs Rituximab Plus Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma | John Leonard | 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological III | Saturday, December 10, 2:15 PM | |
Iberdomide (CC-220) Monotherapy or in Combination with an Anti-CD20 Monoclonal Antibody as Effective Therapy in Patients with Relapsed/Refractory Lymphoma: Early Results from a Phase 1/2 Study | Catherine Thieblemont | 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological III | Saturday, December 10, 3:00 PM | |
Lisocabtagene Maraleucel (liso-cel) versus Standard of Care (SOC) with Salvage Chemotherapy Followed by Autologous Stem Cell Transplantation (ASCT) as Second-line (2L) Treatment in Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL): Primary Analysis of the Randomized, Phase 3 TRANSFORM Study | Jeremy Abramson | 705. Cellular Immunotherapies: Results from CD19-Directed CAR T in treating Aggressive B-cell Lymphomas | Sunday, December 11, 4:30 PM
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Matching-Adjusted Indirect Comparison (MAIC) of Lisocabtagene Maraleucel (Liso-cel) Versus Axicabtagene Ciloleucel (Axi-cel) for Second-line (2L) Treatment of Patients with Refractory/Early Relapsed (R/R) Large B-Cell Lymphoma (LBCL) | Jeremy Abramson
| 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster I | Saturday December 10, 5:30 – 7:30 PM | |
Real-World Treatment Patterns and Costs of Chimeric Antigen Receptor (CAR) T Cell Therapies (CAR T), Polatuzumab Vedotin-piiq (pola), and Tafasitamab-cxix (tafa) in Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) | Fei Fei Liu | 905. Outcomes Research—Lymphoid Malignancies: Health Outcomes in CAR T and Stem Cell Transplantation | Monday, December 12, 5:00 PM | |
Results from OUTREACH: A Phase 2 Study of Lisocabtagene Maraleucel (Liso-cel) Administered as Outpatient (Outpt) or Inpatient (Inpt) Treatment in the Community/Nonuniversity Setting in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) | Yuliya Linhares | 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III | Monday, December 12, 6:00 – 8:00 PM | |
Multiple Myeloma | ||||
Alnuctamab (BMS-986349; CC-93269), a B-cell Maturation Antigen (BCMA) x CD3 2+1 T cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study | Sandy W. Wong | 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Bispecific Monoclonal Antibodies in Myeloma | Saturday, December 10, 1:15 PM | |
KarMMa-2 Cohort 2a: Efficacy and Safety of Idecabtagene Vicleucel in Clinical High-risk Multiple Myeloma Patients with Early Relapse After Frontline Autologous Stem Cell Transplantation | Saad Usmani
| 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: CAR T in Multiple Myeloma and T-cell Therapies After Allo-HCT | Saturday, December 10, 4:00 PM | |
Clinical Activity of BMS-986393 (CC-95266), a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients With Relapsed and/or Refractory (R/R) Multiple Myeloma (MM): First Results From a Phase 1, Multicenter, Open-Label Study | Susan Bal | 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: CAR T in Multiple Myeloma and T-cell Therapies After Allo-HCT | Saturday, December 10, 4:45 PM | |
Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Anti-B-Cell Maturation Antigen (BCMA)-Exposed Cohort of the CC-220-MM-001 Trial | Sagar Lonial | 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster I | Saturday, December 10, 5:30 – 7:30 PM | |
Results From the First Phase 1 Clinical Study of the B-cell Maturation Antigen (BCMA) NEX-T Chimeric Antigen Receptor (CAR) T Cell Therapy CC-98633/BMS-986354 in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM) | Luciano Megala Costa | 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Novel Drugs and Optimized Approaches in Myeloma | Sunday, December 11, 12:15 PM | |
Mezigdomide (CC-92480), a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD), Combined with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Dose-Expansion Phase of the CC-92480-MM-001 Trial | Paul Richardson | 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Novel Drugs and Optimized Approaches in Myeloma | Sunday, December 11, 12:45 PM | |
KarMMa-2 Cohort 2c: Efficacy and Safety of Idecabtagene Vicleucel in Patients with Clinical High-risk Multiple Myeloma due to Inadequate Response to Frontline Autologous Stem Cell Transplantation | Madhav Dhodapkar
| 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II | Sunday, December 11, 6:00 – 8:00 PM | |
Myelodysplastic Syndromes | ||||
Real-World Outcomes of Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Treated with Luspatercept: an Evaluation of US Clinical Practice Utilization and Treatment Patterns | Sudipto Mukherjee | 906. Outcomes Research—Myeloid Malignancies I | Saturday, December 10, 5:00 PM | |
Multiple Episodes of Transfusion Independence with Luspatercept Treatment and the Impact of Dose Escalation in Patients with Lower-Risk Myelodysplastic Syndromes from the MEDALIST Study | Uwe Platzbecker | 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster II | Sunday, December 11, 6:00 – 8:00 PM | |
Overall Survival and Progression-Free Survival of Patients Following Luspatercept Treatment in the MEDALIST Trial | Valeria Santini | 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster I | Sunday, December 11, 5:30 – 7:30 PM | |
Myelofibrosis | ||||
Safety and Efficacy of Fedratinib in Patients with Primary (P), Post-Polycythemia Vera (post-PV), and Post-Essential Thrombocythemia (Post-ET) Myelofibrosis (MF) Previously Treated with Ruxolitinib: Primary Analysis of the FREEDOM Trial | Vikas Gupta | 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I | Saturday, December 10, 5:30 – 7:30 PM | |
BMS-986158, a Potent BET Inhibitor, As Monotherapy and in Combination with Ruxolitinib or Fedratinib in Intermediate- or High-Risk Myelofibrosis: First Results from a Phase 1/2 Study | Rosa Ayala | 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III | Monday, December 12, 6:00 – 8:00 PM |
Bristol Myers Squibb: Creating a Better Future for Cancer Patients
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
BREYANZI U.S. INDICATION
Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy, administered as a defined composition to reduce variability of the CD8 and CD4 component dose. Breyanzi has a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. Breyanzi was previously approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, 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. Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Breyanzi is also approved in Europe, Switzerland, Canada and Japan for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma. For more information, visit clinicaltrials.gov.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES
Cytokine Release Syndrome
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occur in 46% (190/418) of patients, including ≥ Grade 3 CRS (Lee grading system) in 3.1% of patients.
In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days).
In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days).
The most common manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).
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.
Of the 418 patients who received BREYANZI for LBCL, 23% received tocilizumab and/or a corticosteroid for CRS, including 10% who received tocilizumab only and 2.2% who received corticosteroids only.
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 patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% with a median duration of 12 days (range: 1 to 87 days).
In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicities was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days).
In all patients combined receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS.
The most common neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).
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:
Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.
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 patients receiving BREYANZI for LBCL, infections of any grade occurred in 36% 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 occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients with LBCL. 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 patients who received BREYANZI for LBCL, 15 of the 16 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.
Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% of patients with LBCL, and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.
Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI.
In patients receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an adverse reaction in 11% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% 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. 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.
Adverse Reactions
The most common nonlaboratory adverse reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.
The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, hemoglobin 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 four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA
Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. CRS occurred in 85% (108/127) of patients receiving ABECMA. Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time to onset of CRS, any grade, was 1 day (range: 1 - 23 days) and the median duration of CRS was 7 days (range: 1 - 63 days) in all patients including the patient who died. The most common manifestations of CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, 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.
Fifty four percent (68/127) of patients received tocilizumab; 35% (45/127) received a single dose while 18% (23/127) received more than 1 dose of tocilizumab. Overall, across the dose levels, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS received tocilizumab.
Overall rate of CRS was 79% and rate of Grade 2 CRS was 23% in patients treated in the 300 x 106 CAR+ T cell dose cohort. For patients treated in the 450 x 106 CAR+ T cell dose cohort, the overall rate of CRS was 96% and rate of Grade 2 CRS was 40%. Rate of Grade 3 or higher CRS was similar across the dose range. The median duration of CRS for the 450 x 106 CAR+ T cell dose cohort was 7 days (range: 1-63 days) and for the 300 x 106 CAR+ T cell dose cohort was 6 days (range: 2-28 days). In the 450 x 106 CAR+ T cell dose cohort, 68% (36/53) of patients received tocilizumab and 23% (12/53) received at least 1 dose of corticosteroids for treatment of CRS. In the 300 x 106 CAR+ T cell dose cohort, 44% (31/70) of patients received tocilizumab and 10% (7/70) received corticosteroids. All patients that received corticosteroids for CRS also received tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA.
Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated.
Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.
Neurologic Toxicities: 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. CAR T cell-associated neurotoxicity occurred in 28% (36/127) of patients receiving ABECMA, including Grade 3 in 4% (5/127) of patients. 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. The median time to onset of neurotoxicity was 2 days (range: 1 - 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of patients with a median duration of neurotoxicity was 5 days (range: 1 - 61 days). The median duration of neurotoxicity was 6 days (range: 1 - 578) in all patients including those with ongoing neurotoxicity at the time of death or data cut off. Thirty-four patients with neurotoxicity had CRS. Neurotoxicity had onset in 3 patients before, 29 patients during, and 2 patients after CRS. The rate of Grade 3 neurotoxicity was 8% in the 450 x 106 CAR+ T cell dose cohort and 1.4% in the 300 x 106 CAR+ T cell dose cohort. The most frequently reported (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%). Grade 4 neurotoxicity and cerebral edema in 1 patient has been reported with ABECMA in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have been reported 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 and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.
Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA. One patient treated in the 300 x 106 CAR+ T cell 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. The rate of HLH/MAS was 8% in the 450 x 106 CAR+ T cell dose cohort and 1% in the 300 x 106 CAR+ T cell dose cohort. All events of HLH/MAS had onset within 10 days of receiving ABECMA with a median onset of 7 days (range: 4-9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. 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 standards.
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 18884235436.
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. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, preemptive, and/or therapeutic antimicrobials according to standard institutional guidelines.
Febrile neutropenia was observed in 16% (20/127) 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.
Prolonged Cytopenias: Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and ABECMA infusion. In the KarMMa study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. Rate of prolonged neutropenia was 49% in the 450 x 106 CAR+ T cell dose cohort and 34% in the 300 x 106 CAR+ T cell dose cohort. In 83% (43/52) 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 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Median time to cytopenia recovery was similar across the 300 and 450 x 106 dose cohort.
Three patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to institutional guidelines.
Hypogammaglobulinemia: Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with ABECMA. Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dl after infusion in 25% (32/127) of patients treated with ABECMA.
Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG 2% of patients who received INREBIC included anemia (6%), diarrhea (3%), vomiting (3%), and thrombocytopenia (2%).
DRUG INTERACTIONS: Coadministration of INREBIC with a strong CYP3A4 inhibitor increases fedratinib exposure. Increased exposure may increase the risk of adverse reactions. Consider alternative therapies that do not strongly inhibit CYP3A4 activity. Alternatively, reduce the dose of INREBIC when administering with a strong CYP3A4 inhibitor. Avoid INREBIC with strong and moderate CYP3A4 inducers. Avoid INREBIC with dual CYP3A4 and CYP2C19 inhibitor. Coadministration of INREBIC with drugs that are CYP3A4 substrates, CYP2C19 substrates, or CYP2D6 substrates increases the concentrations of these drugs, which may increase the risk of adverse reactions of these drugs. Monitor for adverse reactions and adjust the dose of drugs that are CYP3A4, CYP2C19, or CYP2D6 substrates as necessary when coadministered with INREBIC.
PREGNANCY/LACTATION: Consider the benefits and risks of INREBIC for the mother and possible risks to the fetus when prescribing INREBIC to a pregnant woman. Due to the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with INREBIC, and for at least 1 month after the last dose.
RENAL IMPAIRMENT: Reduce INREBIC dose when administered to patients with severe renal impairment. No modification of the starting dose is recommended for patients with mild to moderate renal impairment. Due to potential increase of exposure, patients with preexisting moderate renal impairment require more intensive safety monitoring, and if necessary, dose modifications based on adverse reactions.
HEPATIC IMPAIRMENT: Avoid use of INREBIC in patients with severe hepatic impairment.
Please see full Prescribing Information, including Boxed WARNING, and Summary of Product Characteristics for INREBIC.
ONUREG U.S. INDICATION
ONUREG® (azacitidine tablets) is approved in the U.S. for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy.
U.S. IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONS
LACTATION
Please see full Prescribing Informationfor ONUREG.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that the product candidates described in this release may not receive regulatory approval for the indications described in this release and, if approved, whether such product candidates for such indications will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2021, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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Source: Bristol Myers Squibb