Data from pivotal KarMMa study to be presented at ASCO21 show 24.8-month median overall survival in triple-class exposed multiple myeloma

With more than 24-month median follow-up, results represent longest follow-up to date from a global clinical trial of a CAR T cell therapy in multiple myeloma with 73% overall response rate and responses ongoing

Analysis of characteristics of neurotoxicity (NT) observed in KarMMa study reinforce well-understood safety profile of Abecma with mostly Grade 1/2 occurrences of NT having early onset and resolution

PRINCETON, NJ & CAMBRIDGE, MA, USA I May 19, 2021 I Bristol Myers Squibb (NYSE: BMY) and bluebird bio, Inc. (Nasdaq: BLUE) today announced new data and analyses from the pivotal KarMMa study evaluating Abecma (idecabtagene vicleucel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, to be presented at the American Society of Clinical Oncology (ASCO) 2021 Virtual Annual Meeting. These data include updated results (Abstract #8016) and analysis of characteristics of treatment-associated neurotoxicity (Abstract #8036) from the KarMMa study of Abecma in triple-class exposed relapsed or refractory multiple myeloma. The updated KarMMa results will be shared in a poster discussion on June 4 at 9:00 a.m. EDT.

In the pivotal KarMMa study, 128 patients with relapsed or refractory multiple myeloma who had received at least three prior treatment regimens including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody were treated with Abecma at the target dose levels of 150 x 106 to 450 x 106 CAR-positive T cells. Patients had a median of six prior regimens (range: 3-16), with 84% (108/128) of patients being triple-class refractory.1

With a median follow-up of 24.8 months in 128 patients treated with Abecma, representing the longest follow-up to date from a global clinical trial of a CAR T cell therapy in multiple myeloma, the overall response rate (ORR; primary endpoint) remained consistent, with 73% (94/128) of patients achieving a partial response or better and 33% (42/128) of patients achieving a complete response (CR) or better. Responses were similar for patients regardless of number of prior lines of therapy. Median duration of response was 10.9 months and increased with depth of response, with a median duration of response of 21.5 months for patients who achieved a CR or better. Median progression-free survival (PFS) was 8.6 months (95% CI: 5.6-11.6). Overall survival (OS), a secondary endpoint of the study, showed an 18-month event-free rate for OS of 65% and a 24-month event-free rate for OS of 51% among all treated patients. The median OS was 24.8 months (95% CI: 19.9-31.2), and these survival data continue to mature.1

Cytopenias (97%) and cytokine release syndrome (CRS; 84%) were the most common adverse events of any grade. Occurrences of CRS were mostly low grade (Grade 1/2: 78%). Investigators reported Grade 3 CRS in five patients (4%), Grade 4 CRS in one patient, and Grade 5 CRS in one patient. Investigator-reported neurotoxicity (NT) of any grade was reported in 18% (23/128) of patients, with five cases (4%) of Grade 3 NT and no Grade 4/5 events. The safety profile of Abecma was similar regardless of number of prior lines of therapy.1

“Longer-term data from our pivotal KarMMa study for Abecma further demonstrate the potential of this first-in-class BCMA-directed CAR T cell therapy to deliver clinically meaningful outcomes with a predictable safety profile for patients with relapsed or refractory multiple myeloma, underscoring the strength of this novel and individualized treatment,” said Kristen Hege, senior vice president, Early Clinical Development, Hematology/Oncology & Cell Therapy. “Building on our legacy in multiple myeloma and other hematologic malignancies, Bristol Myers Squibb will continue to evaluate Abecma for patients with critical unmet need.”

“The pivotal KarMMa study provides the longest follow-up for any CAR T cell therapy evaluated in a global clinical trial in multiple myeloma and, with a median follow-up of 24.8 months, we are continuing to see durability of responses and long-term survival across the study population, regardless of number of prior lines of therapy,” said Anna Truppel-Hartmann, Vice President Clinical Development Oncology, bluebird bio. “The results we are observing in patients who are heavily pre-treated and triple-class exposed validates the transformative potential of the newly approved Abecma in relapsed or refractory myeloma. We look forward to advancing our broad clinical development program to bring this therapy to even more patients who may benefit.”

In a separate analysis from the KarMMa study evaluating the characteristics of treatment-associated NT that occurred in 18% (23/128) of patients, NT events were mostly low-grade, occurring early with generally short duration, reinforcing the predictable and well-established safety profile of Abecma. Maximum Grade 1, 2 and 3 NT was reported in 11 (9%), seven (5%), and five (4%) of 128 patients treated with Abecma, respectively. Median time to onset of NT was two days (range: 1-10 days) with a median duration of 2.5 to 8.5 days (range: 1-26 days). All cases of NT were proximal to CRS events with the start of NT overlapping with or occurring within one week of the start of a CRS event. For patients who achieved a response, ORR and duration of response were similar among patients who did (n=17) and did not (n=77) experience NT (74% and 10.0 months, and 73% and 11.0 months, respectively).2

“With these updated data from the KarMMa study, we are seeing the longest follow-up from a global clinical trial for an anti-BCMA CAR T cell therapy in multiple myeloma, which continues to reinforce that ide-cel provides deep and durable responses with the potential for long-term disease control and survival in patients with triple-class exposed relapsed or refractory multiple myeloma,” said Larry D. Anderson Jr., M.D., Ph.D., associate professor, Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center. “Additionally, the benefit-risk profile of ide-cel is further reinforced by the updated data with low rates of severe CRS and our separate analysis showing low rates of mostly low-grade neurotoxicity in the KarMMa study, confirming that ide-cel represents an important treatment option for patients who have been exposed to many prior therapies.”

Abecma is the first BCMA-directed CAR T cell therapy to be approved by the U.S. Food and Drug Administration (FDA), and is 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. The U.S. Prescribing Information for Abecma has a BOXED WARNING for the risks of cytokine release syndrome (CRS), neurologic toxicities (NT), Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), and Prolonged Cytopenia.3

Bristol Myers Squibb’s Marketing Authorization Appplication for Abecma is currently under review by the European Medicines Agency. Regulatory applications for Abecma are also currently under review in Canada, Switzerland and Japan.

Disclosure: Dr. Anderson has served on advisory boards for Bristol Myers Squibb.

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.

About Abecma

Abecma is the first-in-class B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy approved in the U.S. 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. Abecma recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement with Bristol Myers Squibb and bluebird bio.

Bristol Myers Squibb and bluebird bio’s broad clinical development program for Abecma includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4, KarMMa-7) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

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.

Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, we’re developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, we’re working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, β-thalassemia and multiple myeloma using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

References

  1. Anderson LD, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: updated KarMMa results. ASCO 2021 Virtual Scientific Program. Abstract #8016.
  2. Manier S, et al. Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121) in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II KarMMa study. ASCO 2021 Virtual Scientific Program. Abstract #8036.
  3. Abecma Prescribing Information. Bristol Myers Squibb; March 2021.

SOURCE: Bristol Myers Squibb