The FDA’s Oncologic Drugs Advisory Committee (ODAC) will review data related to a supplemental biologics license application (sBLA) for idecabtagene vicleucel (ide-cel; Abecma; Bristol Myers Squibb, 2seventybio), a marketed BCMA-directed chimeric antigen receptor (CAR) T-cell therapy, in a newly announced advisory committee (AdComm) meeting.1 As a result of the AdComm meeting, which has not yet been scheduled for a specific date, the Prescription Drug User Fee Act (PDUFA) action date for the sBLA, which was originally scheduled for December 16, 2023, has been pushed back to an as yet unspecified later date.
The sBLA was submitted with the intention of expanding ide-cel from its current FDA-approved indication, which covers adults with triple-class exposed relapsed/refractory multiple myeloma (r/r MM) who have received 4 or more previous lines of treatment, to earlier-line settings. Bristol Myers Squibb (BMS) and 2seventybio expect that the AdComm meeting will be focused on a review of overall survival (OS) data from the phase 3 KarMMa-3 clinical trial (NCT03651128) evaluating ide-cel in patients with r/r MM that have received 2 to 4 previous lines of treatment. The OS results constituted a secondary end point for KarMMa-3; the trial’s primary end point was previously met when a statistically significant improvement in progression-free survival (PFS) was demonstrated in comparison to standard-of-care (SOC) regimens. BMS and 2seventybio noted that final PFS data and new interim OS data from KarMMa-3 will be presented on December 11 at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 9-12, 2023, in San Diego, California. The companies also stated that the result of the AdComm meeting will not affect the status of ide-cel's currently approved indication.
Earlier PFS and overall response rate (ORR) results from KarMMa-3 were previously reported this year in a late-breaking session at the 2023 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Orlando, Florida, February 15-19, 2023.2 Among the patients in the ide-cel arm, PFS ranged from 11.8 to 16.1 months (median, 13.3, 95% CI) versus PFS that ranged from 3.4 to 5.9 months (median, 4.4, 95% CI) for the patients in the SOC arm [HR, 0.49 (95% CI, 0.38-0.65); P < .0001 based on stratified log-rank test]. Meanwhile, the ORR for patients in the ide-cel arm was 71% (95% CI, 66-77), while the ORR for patients in the SOC arm was 42% (95% CI, 33-50) and 51 patients (20%) in the ide-cel arm achieved a complete response (CR) or better and minimal residual disease (MRD)-negative status (95% CI, 15.2-25.0) while only 1 patient (1%) in the SOC arm achieved a CR or better and MRD-negative status (95% CI, 0-2.2). In terms of safety, BMS and 2seventybio reported alongside the announcement of the new Adcomm meeting that safety findings in KarMMa-3 have been in-line with expectations regarding the previously established safety-profile of the CAR-T.1
“The toxicity was actually similar in older patients and in younger patients,” Sergio Giralt, MD FACP, FASTCT, Memorial Sloan Kettering Cancer Center, who presented the data at the 2023 Tandem Meetings, said in response to an audience question following his presentation.2 “I do think it's important to recognize that there were there were 3% fatal events in the ide-cel arm versus 1% in the standard control. These were primarily sepsis. There was 1 case of severe fatal CRS that was associated with Candida sepsis and another case of CRS that also was fatal. I do think that there was a learning curve as we started doing this; particularly in patients with high tumor burden, we very rapidly decided that we needed to intervene early with steroids and tocilizumab at the first sign of CRS. Particularly one of the things we learned is if CRS occurs within the first 24 hours, those patients were at high risk of developing severe CRS, and we needed to intervene early.”
- The FDA's Oncologic Drugs Advisory Committee (ODAC) will review data on idecabtagene vicleucel (ide-cel), a BCMA-directed CAR-T therapy developed by Bristol Myers Squibb and 2seventybio, for potential expansion into earlier-line settings for triple-class exposed relapsed/refractory multiple myeloma (r/r MM).
- The Prescription Drug User Fee Act (PDUFA) action date for ide-cel's supplemental biologics license application (sBLA) has been postponed from the originally scheduled date of December 16, 2023, due to the upcoming advisory committee meeting.
- BMS and 2seventybio noted that final PFS data and new interim OS data from KarMMa-3 will be presented on December 11 at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 9-12, 2023, in San Diego, California.
In addition to KarMMa-3, ide-cel is also being evaluated for its potential in early-line settings in 2 other ongoing clinical trials: KarMMa-2 (NCT03601078) and KarMMa-9 (NCT06045806). The phase 2 KarMMa-2 trial is evaluating ide-cel in patients with r/r MM who have progressed within 18 months of initial treatment. On the other hand, the phase 3 KarMMa-9 clinical trial (NCT06045806) is evaluating ide-cel in patients with newly diagnosed MM who achieved a suboptimal response to autologous stem cell transplantation.
1. Bristol Myers Squibb and 2seventy bio Provide Update on U.S. FDA Review of sBLA for Abecma (idecabtagene vicleucel) in Earlier Lines of Therapy for Triple-Class Exposed Relapsed or Refractory Multiple Myeloma. News release. 2seventy bio, Inc. November 20, 2023. Accessed November 20, 2023. https://ir.2seventybio.com/news-releases/news-release-details/bristol-myers-squibb-and-2seventy-bio-provide-update-us-fda
2. Giralt S, Ailawadhi S, Arnulf B, et al.Idecabtagene vicleucel (ide-cel) versus standard regimens in patients with triple-class–exposed relapsed and refractory multiple myeloma: KarMMa-3, a phase 3 randomized controlled trial. Presented at: 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR. February 15-19, 2023; Orlando, FL. Abstract LBA1