The FDA decided last month to convene an advisory committee to discuss the companies’ proposed use of Abecma in earlier lines of treatment for multiple myeloma. Data presented Monday at the American Society of Hematology annual meeting provides a clue as to why.
Pictured: Bristol Myers Squibb sign on side of glass building/iStock, JHVEPhoto
The FDA’s November decision to delay Abecma (idecabtagene vicleucel) for earlier line treatment in multiple myeloma is starting to become clearer. New trial data from Bristol Myers Squibb and 2seventy bio were presented at the American Society of Hematology meeting on Monday and it looks like overall survival data is potentially concerning.
In the Phase III KarMMa-3 study for multiple myeloma, the partner’s CAR-T cell therapy appeared to cut patient’s risk of death by 31% compared to those on standard of care. However, this result was from a statistical adjustment accounting for over half of patients from the standard of care arm crossing over to the Abecma arm after cancer progression.
The unadjusted study results showed no significant advantage for extending patients’ lives when compared to the standard of care arm, according to Monday’s updated interim analysis. Median overall survival (OS) was longer in the Abecma arm—41.4 months versus 37.9 months in the control arm.
Patients receiving the CAR-T cell therapy did see a significant improvement in progression-free survival (PFS) compared to standard treatment. Abecma treatment resulted in a 51% reduction in the risk of progression or death after a longer follow-up. PFS came in at 13.8 months in the treatment arm versus 4.4 months in the control.
In April 2023, BMS and 2seventy bio’s application to push the CAR-T therapy up earlier in the treatment line was accepted. However, the FDA decided last month that it would convene its Oncologic Drugs Advisory Committee to discuss the application before making a decision.
The agency was initially expected to make a decision on Abecma’s most recent BLA by December 16. But with the FDA yet to set a date for the advisory committee to convene, a delay is inevitable and a decision on the application will not be made by the PDUFA target action date.
In the companies’ announcement last month, BMS and 2seventy bio noted that the advisory committee is likely to focus on OS, a key secondary outcome of KarMMa-3.
During a presentation at the American Society of Hematology meeting on Monday, Paula Rodríguez Otero from Clínica Universidad de Navarra in Spain suggested some explanations for the OS results. Seventeen patients who were supposed to be in the Abecma arm died before receiving the therapy compared to zero in the control. Excluding those patients, the Abecma arm had a 17% reduction in the risk of death, according to Fierce Pharma.
Abecma was originally approved in March 2021 as the first cell-based gene therapy for the treatment of adults with multiple myeloma. Its current label is limited to patients with at least four prior lines of therapy, including a proteasome inhibitor, an anti-CD38 monoclonal antibody and an immunomodulatory agent.
CAR-T therapies like Abecma, J&J’s Carvykti, Novartis’ Kymriah and others have recently come under scrutiny with the FDA. Last month, the agency launched an investigation into the risk of malignancies in patients who received BCMA- or CD19-directed CAR-T cell therapies. While acknowledging the overall benefits of these treatments outweigh their potential risks, the FDA is “evaluating the need for regulatory action.”
Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.
