ODAC Meeting to Discuss Ide-Cel for Earlier Lines of Triple-Class Exposed R/R Multiple Myeloma Treatment

The FDA’s Oncologic Drugs Advisory Committee (ODAC) is meeting this week to discuss the supplemental Biologics License Application (sBLA) for idecabtagene vicleucel (Abecma; Bristol Myers Squibb; 2seventybio for triple-class exposed relapsed or refractory multiple myeloma (r/r MM).¹

The ODAC meeting will review data from the pivotal Phase 3 KarMMa-3 trial (NCT03651128) that may support the sBLA, expanding the currently approved indication for patients who have received 4 or more previous lines of treatment to earlier lines of therapy.

Bristol Myers Squibb (BMS) and 2seventybio announced the ODAC meeting in November 2023 along with a delay in Prescription Drug User Fee Act (PDUFA) action date, which was originally scheduled for December 16, 2023, and has been pushed back to an unspecified later date.²

The companies expect that the meeting will focus on a review of overall survival (OS) data from KarMMa-3, one of the trial’s secondary end points. 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, an improvement that has since been reinforced by longer follow-up data.

WATCH NOW: Paula Rodríguez Otero, MD, PhD, on Demonstrating Ide-cel's PFS Superiority in Triple-Class-Exposed R/R Multiple Myeloma

The most updated data from KarMMa-3 were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California, by Paula Rodríguez Otero, MD, PhD, a hematologist at the University of Navarra.³

Patients treated with ide-cel had a median OS of 41.4 months (95% CI, 30.9-not reached [NR]) and those treated with SOC had a median OS of 37.9 months (95% CI, 23.4-NR; hazard ratio, 1.01 [95% CI, 0.73-1.40]). Prespecified sensitivity analyses adjusting for crossover revealed a median OS of 41.4 months with ide-cel (95% CI, 30.9-NR) and 23.4 months (95% CI, 17.9-NR) with SOC (HR, 0.69 [95% CI, 0.45-1.09]). Historically, median OS for patients with triple-class exposed r/r MM is approximately 13 months.³

“After a median follow up of 31 months, ide-cel continued to show significantly longer and clinically meaningful improvement in progression-free survival versus the standard regimens,” Otero told CGTLive.

Complicating BMS and 2seventybio’s bid for an earlier line indication is the recent FDA announcement of investigations into the risk of T-cell malignancies in patients that have received B cell maturation antigen (BCMA)-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies, and the subsequent updated black box warning for ide-cel reading “T cell malignancies have occurred following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including Abecma. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.”^4,5

REFERENCES

1. Bristol Myers Squibb and 2seventy bio Share Update on U.S. FDA Oncologic Drugs Advisory Committee Meeting for Abecma in Triple-Class Exposed Multiple Myeloma Based on KarMMa-3 Study. News release. Bristol Myers Squibb. February 5, 2024. https://finance.yahoo.com/news/bristol-myers-squibb-2seventy-bio-115900981.html
2. 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

3. Otero PR, Ailawadhi S, Arnulf B, et al. Idecabtagene vicleucel (ide-cel) versus standard (std) regimens in patients (pts) with triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): updated analysis from KarMMa-3. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #1028 
4. FDA investigating serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. News release. FDA. November 28, 2023. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous?utm_medium=email&utm_source=govdelivery
5. Safety Labeling Change Notification Letter - ABECMA (idecabtagene vicleucel). News release. FDA. January 19, 2024. https://www.fda.gov/media/175623/download?attachment