FDA Approves First Anti-BCMA CAR T-Cell Therapy for Relapsed, Refractory Multiple Myeloma
In a clinical trial of idecabtagene vicleucel in multiple myeloma, the overall response rate for the efficacy evaluable population was 72%, and 28% of participants achieved a stringent complete response.
Officials with the FDA approved idecabtagene vicleucel (Abecma, Bristol Myers Squibb) for the treatment of relapsed or refractory multiple myeloma after 4 or more prior lines of therapy. It is the first-in-class B-cell maturation agent (BCMA)-directed personalized immune cell therapy delivered as a 1-time infusion for triple-class exposed patients.
Despite developments in effective treatments, multiple myeloma is an incurable disease characterized by periods of remissions and relapse. According to a press release, most patients experience relapse following initial therapies and the depth and duration of response decrease with each successive treatment, as well as survival outcomes.
Notably, patients who have been exposed to all 3 major drug classes (triple-class exposed), including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, tend to have poor clinical outcomes with very low response rates between 20% and 30%, short durations of response between 2 to 4 months, and poor survival rates, according to the release.
Idecabtagene vicleucel has a recommended dose range of 300 to 460 x 106 chimeric antigen receptor (CAR)-positive T cells, according to the release. As an anti-BCMA CAR T-cell therapy, it binds to BCMA, which is nearly universally expressed on cancer cells in multiple myeloma and leads to the death of BCMA-expressing cells.
The approval is based on data from the phase 2 KarMMa trial of 127 triple-class exposed patients with relapsed or refractory multiple myeloma. According to the press release, the overall response rate for the efficacy evaluable population was 72%, and 28% of participants achieved a stringent complete response (sCR). The patients had a median time to response of 30 days and median duration of response of 11 months for all responders and 19 months for those who achieved sCR.
“In the KarMMa study, ide-cel elicited rapid responses in the majority of patients, and these deep and durable responses were observed in patients with triple-class exposed and refractory multiple myeloma,” said Nikhil C. Munshi, MD, associate director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, in the press release.
The safety profile was well-established with mostly low-grade occurrence of cytokine release syndrome (CRS) and neurotoxicity, as well as predictable early onset and resolution. CRS of any grade occurred in 85% of patients and grade 3 or higher CRS occurred in 9%. Grade 5 CRS was reported in just 1 patient. The most common manifestations of CRS were pyrexia, hypotension, tachycardia, chills, hypoxia, fatigue, and headache.
Neurotoxicity of any grade occurred in 28% of patients, including grade 3 or higher events in 4% and 1 patient who had ongoing grade 2 neurotoxicity at the time of death. The median time to onset was 2 days and it resolved in 33 of 36 patients, with a median time to resolution of 5 days.
The most common types of nonlaboratory adverse reactions included CRS, infections, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite. Serious adverse reactions occurred in 67% of patients, with the most common being CRS (18%), general physical health deterioration (10%), pneumonia (12%), infections (19%), viral infections (9%), sepsis (7%), and febrile neutropenia (6%).
“As a treating physician, I often work with patients with relapsed or refractory multiple myeloma who are in critical need of new therapies,” Munshi said in the press release. “Now, with the approval of ide-cel as the first anti-BCMA CAR T-cell therapy, we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion.”
US Food and Drug Administration Approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the First Anti-BCMA CAR T Cell Therapy for Relapsed or Refractory Multiple Myeloma [news release]. Bristol Myers Squibb; March 26, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-and-bluebird-bios-Abecma-idecabtagene-vicleucel-the-First-Anti-BCMA-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx. Accessed March 30, 2021.