FDA ODAC to Review Ide-Cel Data in Multiple Myeloma

CAR T-cell attack cancer cell and healthy cells © LASZLO - stock.adobe.com

• The FDA will review data on overall survival (OS) of idecabtagene vicleucel (ide-cel; Abecma), for multiple myeloma on March 15, 2024, representing a critical step in the approval process for this chimeric antigen receptor (CAR) T-cell therapy.
• The review comes after final progression-free survival (PFS) and interim overall survival (OS) data showed promising results.
• The review also follows the announcement of the FDA’s investigation into secondary malignancies associated with CAR T-cell therapies on November 28, 2023.

The FDA’s Oncologic Drug Advisory Committee (ODAC) will convene on March 15, 2024, to review data from the phase 3 KarMMa-3 study (NCT03651128) of ide-cel in patients with triple class-exposed relapsed/refractory (R/R) multiple myeloma.¹ It is anticipated that the data will be related to the key secondary end point of OS that were presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

The supplemental biologics license application (sBLA) of ide-cel had a Prescription Drug User Fee Act target action date of December 16, 2023. On November 20, 2023, the FDA announced that it would review the application at an ODAC meeting and a decision on the sBLA would not be made by the target action date.²

Further, on November 28, 2023, the FDA announced it would investigate reports of secondary malignancies following treatment with CAR T-cell therapies, including ide-cel.³

At ASH, investigators of the KarMMA-3 study presented final progression-free survival (PFS) and interim OS findings. With a median follow-up of 30.9 months, range, 12.7–47.8), investigators observed a 51% reduction in risk of disease progression or death (HR, 0.49; 95% CI, 0.38-0.63). KarMMA-3 also represented the longest follow-up time of a randomized phase 3 study of a CAR T-cell therapy in this intent-to-treat population.⁴ The median PFS for patients treated with ide-cel was 13.8 months (range, 11.8-16.1) vs 4.4 months (range, 3.4-5.8) with standard regimens.⁵ The median OS was 41.4 months in the ide-cel arm vs 37.9 months in the control arm.⁶

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. February 5, 2024. Accessed February 5, 2024. http://tinyurl.com/msmpbezm

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. November 20, 2023. Accessed February 5, 2024. http://tinyurl.com/mryh5zvh

3. FDA investigating serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. U.S. Food & Drug Administration. November 28, 2023. Accessed February 5, 2024. http://tinyurl.com/yvjmebpc

4. Abecma delivers sustained progression-free survival versus standard regimens in earlier lines of therapy for relapsed and refractory multiple myeloma based on longer-term follow-up from KarMMa-3. News release. December 11, 2023. Accessed February 5, 2024. http://tinyurl.com/3kwdr5ks

5. Rodriguez Otero P, Ailawadhi S, Arnulf B, et al. Idecabtagene cicleucel (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. Blood 2023; 142 (Supplement 1): 1028. doi: 10.1182/blood-2023-178933

6. BMS, 2seventy bio present Abecma survival data at ASH ahead of Adcomm. News release. December 12, 2023. Accessed February 5, 2023. http://tinyurl.com/426y4n7v