ODAC Meeting to Discuss Ide-Cel for Earlier Lines of Triple-Class Exposed R/R Multiple Myeloma Treatment
The committee is set to discuss idecabtagene vicleucel’s sBLA on March 15, 2024.
Paula Rodríguez Otero, MD, PhD
(Credit: Clinica Universidad de Navarra)
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.
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
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