Bristol Myers Squibb and bluebird bio Announce Two-Year Follow-Up Data from Pivotal KarMMa Study of Abecma (idecabtagene vicleucel), the First-in-Class Anti-BCMA CAR T-Cell Therapy, Demonstrating Deep, Durable Responses and Predictable Safety in Relapsed/Refractory Multiple Myeloma

May 21, 2021 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) and partner bluebird bio recently announced new data and analyses from the pivotal Phase II KarMMa study (NCT03361748), which evaluated the efficacy and safety of Abecma (idecabtagene vicleucel, ide-cel), an anti-B-cell maturation antigen (anti-BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of relapsed/refractory multiple myeloma (R/R MM).

This update presents results with a follow-up of more than 2 years,Represents the global ... to date for a CAR-T cell therapy for the treatment of multiple myeloma (MM)Clinical Trialof the longest follow-up.Long-term data from the KarMMa study continue to show: with a median follow-up exceeding 2 years,Abecma Demonstrates Durable Efficacy and Predictable Safety in Patients with R/R MM. Among patients who had previously received three classes of therapy,Median overall survival (OS) was 24.8 months, overall response rate (ORR) was 73%, with durable responses.. The analysis of the neurotoxicity (NT) profile observed in this study reinforces the well-established safety profile of Abecma,NT is predominantly grade 1/2, with early onset and rapid resolution.

These long-term data further demonstrate that Abecma provides clinically meaningful outcomes and a predictable safety profile for the R/R MM patient population, highlighting the advantages and transformative potential of this novel personalized therapy.

Abecma is a first-in-class, BCMA-directed, personalized cellular immunotherapy. BCMA is a protein that is almost universally expressed on multiple myeloma cancer cells. As an anti-BCMA CAR-T cell therapy, Abecma recognizes and binds to BCMA, leading to the death of BCMA-expressing cells.

Abecma is the world's first regulatory-approved BCMA-directed CAR-T cell therapy.. March 2021, the United StatesFDAApproved Abecma for the treatment of adult patients with R/R MM. The recommended dose is 300–460 × 10^6 CAR-positive T cells, indicated for the treatment of adult patients with R/R MM who have received four or more prior lines of therapy (including three drug classes: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies).

The market approval of Abecma will provide these patients with a new, effective,Personalized Treatment Regimen: Rapid, Deep, and Durable Remission Achieved with a Single Infusion. In clinical studies, the safety of Abecma has been well established in treated patients, with cytokine release syndrome (CRS) and neurotoxicity (NT) predominantly low-grade, exhibiting predictable early onset and rapid resolution.

The KarMMa study was conducted in 128 adult patients with relapsed or refractory multiple myeloma (R/R MM) who had received at least 3 prior classes of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody) and were refractory to their most recent therapy. In the study, these patients received CAR-positive T-cell therapy with Abecma at doses ranging from 150 to 460 × 10^6. Among these patients, the median number of prior lines of therapy was 6 (range: 3–16), and 84% (108/128) were triple-class refractory.

Among 128 patients treated with Abecma, with a median follow-up of 24.8 months, the overall response rate (ORR; primary endpoint) was sustained, with 73% (94/128) of patients achieving a partial response or better and 33% (42/128) achieving a complete response (CR) or better. Responses were similar regardless of the number of prior lines of therapy. The median duration of response (DOR) was 10.9 months, increasing with depth of response, with a median DOR of 21.5 months for patients achieving 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, demonstrated an 18-month event-free survival rate of 65% and a 24-month event-free survival rate of 51% across all treated patients. Median OS was 24.8 months (95% CI: 19.9–31.2), and these survival data continue to mature.

Cytopenias (97%) and cytokine release syndrome (CRS, 84%) were the most common adverse events of any grade. Most CRS events were low-grade (Grade 1/2: 78%). Researchers reported Grade 3 CRS in 5 patients (4%), Grade 4 CRS in 1 patient, and Grade 5 CRS in 1 patient. Neurological toxicity (NT) of any grade occurred in 18% (23/128) of patients, including 5 patients (4%) with Grade 3 NT; no Grade 4/5 events were reported. The safety profile of Abecma was similar regardless of the number of prior treatment regimens.

In a separate analysis of the KarMMa study, the characteristics of treatment-related neurotoxicity (NT) occurring in 18% (23/128) of patients were evaluated. NT events were predominantly low-grade, with early onset and short duration, further reinforcing the predictable and well-established safety profile of Abecma. Among the 128 patients treated with Abecma, 11 (9%), 7 (5%), and 5 (4%) experienced grade 1, grade 2, and grade 3 NT, respectively. The median time to NT onset was 2 days (range: 1–10 days), and the median duration was 2.5–8.5 days (range: 1–26 days). All NT cases occurred in close temporal proximity to cytokine release syndrome (CRS) events, with NT onset overlapping with or occurring within one week following CRS onset. Overall response rate (ORR; 74% vs 73%) and duration of response (DOR; 10.0 months vs 11.0 months) were comparable between patients who experienced NT (n=17) and those who did not (n=77). (Bioon.com)

Original Source: Long-Term Data from Pivotal KarMMa Study Continue to Demonstrate Deep and Durable Responses and Predictable Safety Profile with Bristol Myers Squibb and bluebird bio’s Abecma (idecabtagene vicleucel) in Relapsed or Refractory Multiple Myeloma