FDA Approves CAR T-Cell Therapy Idecabtagene Vicleucel for Previously Treated Multiple Myeloma

The approval of idecabtagene vicleucel was supported by results from the phase 2 KarMMa trial, which evaluated the safety and efficacy of idecabtagene vicleucel (ide-cel) in patients who had received at least 3 prior regimens and were refractory to their last regimen per IMWG criteria.

The FDA has granted approval to the biologics license application (BLA) for the first B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell immunotherapy idecabtagene vicleucel (Abecma; ide-cel) for the treatment of adult patients with multiple myeloma who have received at least 4 prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, according to the co-developers of the agent, Bristol Myers Squibb and bluebird bio.1

“CAR T-cell therapies have shown transformational potential for the treatment of hematologic malignancies, and we, with our partners at bluebird bio, are proud to bring the first CAR T-cell therapy to appropriate triple-class exposed patients with relapsed or refractory multiple myeloma, offering the chance for durable response,” Samit Hirawat, MD, chief medical officer of Bristol Myers Squibb, said in a press release. “Bristol Myers Squibb is now the only company with 2 approved CAR T-cell therapies with distinct targets of CD19 and BCMA. As our second FDA-approved CAR T-cell therapy, Abecma underscores our commitment to deliver on the promise of cell therapies for patients who are battling aggressive and advanced blood cancers with limited effective treatment options.”

The approval was supported by results from the single-arm, multicenter, pivotal phase 2 KarMMa trial (NCT03361748), which evaluated the safety and efficacy of ide-cel in patients who had received at least 3 prior regimens for multiple myeloma and were refractory to their last regimen per International Myeloma Working Group (IMWG) criteria.2 Results of the trial were published in the New England Journal of Medicine earlier this year and data regarding secondary quality-of-life domains were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.3,4

Patients enrolled in the trial had received at least 3 prior regimens and were refractory to their last regimen per IMWG criteria. A total of 140 patients were enrolled, of whom 128 received ide-cel.

At the data cutoff of October 14, 2020, median follow-up was 13.3 months. The overall response rate (ORR) was 73% and median progression-free survival (PFS) was 8.8 months (95% CI, 5.6-11.6). Most patient subgroups had an ORR of at least 50%, including older and high-risk patients. Notably, both ORR and PFS increased with a higher dose.

Median peak CAR T-cell expansion occurred after 11 days and persistence was durable. Importantly, CAR T-cells were detected in 29 of 49 patients (59%) and 4 of 11 patients (36%) at 6 and 12 months, respectively.

Regarding safety, the most common any-grade adverse events (AEs) were cytopenias (neutropenia, 91%; thrombocytopenia, 63%) and cytokine release syndrome (CRS; 84%). Neurotoxicity also developed in 23 patients (18%). Ide-cel now carries a black box warning for CRS, neurotoxic events, and prolonged cytopenias as well as hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

Secondary quality-of-life (QOL) domain analyses were performed after the cutoff date and included patients with at least 10 months of follow-up. By the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life C30 (QLQ-C30), patients showed a clinically meaningful improvement in most functioning and symptom subscale scores from baseline to month 3 through 15 with statistical significance (<.05) reached at various time points for different subscales throughout the follow-up period.

“These data confirm that in [patients with] triple-class exposed relapsed/refractory myeloma, the clinical benefits associated with ide-cel treatment provide clinically meaningful health-related QOL improvements without compromising any HRQOL domains,” Nina Shah, MD, hematologist, oncologist, and multiple myeloma investigators at the University of California San Francisco, said during a presentation of the data during the ASH meeting.

Ide-cel was granted breakthrough therapy designation (BTD) by the FDA, as well as priority medicines (PRIME) designation and validation of its marketing authorization application (MAA) by the European Medicines Agency for relapsed and refractory multiple myeloma. Additionally, Bristol Myers Squibb indicated plans for regulatory submissions of ide-cel in markets outside the United States and European Union in the future.


1. U.S. 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. FDA. Published March 26, 2021. Accessed March 27, 2021. https://bwnews.pr/3w4Fa72

2. U.S. Food and Drug Administration (FDA) Accepts for Priority Review Bristol Myers Squibb and bluebird bio Application for Anti-BCMA CAR T Cell Therapy Idecabtagene Vicleucel (Ide-cel, bb2121). News release. Bristol Myers Squibb and bluebird bio. Published September 22, 2020. Accessed February 10, 2021. https://news.bms.com/news/corporate-financial/2020/U.S.-Food-and-Drug-Administration-FDA-Accepts-for-Priority-Review-Bristol-Myers-Squibb-and-bluebird-bio-Application-for-Anti-BCMA-CAR-T-Cell-Therapy-Idecabtagene-Vicleucel-Ide-cel-bb2121/default.aspx

3. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi: 10.1056/NEJMoa2024850

4. Shah N, Delforge M, San-Miguel J, et al. Secondary quality-of-life domains in patients with relapsed and refractory multiple myeloma treated with BCMA-directed CAR T cell therapy idecabtagene vicleucel (ide-cel; bb2121): results from the Karmma clinical trials. Presented at: 2020 ASH Annual Meeting & Exposition; December 5-8, 2020; Virtual. Poster 437. https://ash.confex.com/ash/2020/webprogram/Paper136665.html