Abecma backed to permit earlier access for R/R Multiple Myeloma Patients
The majority of the Oncologic Drugs Advisory Committee (ODAC) voted to support supplemental biologics license application (sBLA) 125736/218 for Abecma (idecabtagene vicleucel [ide-cel), submitted by Celgene Corporation (Celgene), a Bristol-Myers Squibb Company, for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody (mAb).
The proposed indication would provide access to ide-cel earlier, which the panel agreed was an important option for patients to enhance their quality of life despite a lack of clarity—in the context of prolonged PFS—about whether earlier treatment was better in the sponsor’s study. While the ide-cel arm was associated with a risk of early death, the ODAC generally agreed that the cause of the deaths was unclear and could not be attributed to the therapy exclusively.
To support the sBLA, the sponsor submitted results from KarMMa-3, which met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) in participants randomized to the ide-cel arm compared to participants randomized to the control arm (standard of care [SOC]). The study included a crossover from the SOC arm to ide-cel treatment upon disease progression at the investigator’s request if participants met the eligibility criteria to receive ide-cel. The committee generally agreed that the crossover may have contributed to uncertainty about whether earlier treatment with ide-cel was better than or similar to later treatment and whether early deaths could be due to ide-cel treatment. However, they commended the sponsor’s patient-centered trial design, which provided participants with access to ide-cel despite initially being randomized to SOC.
Proposed Indication
Abecma (ide-cel) for the treatment of adult patients with RRMM who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 mAb.
Proposed Dose
Ide-cel 300-510 x 106 CAR-positive T cells per single-dose intravenous (IV) infusion.
Abecma has been approved in several other regions, including the European Union (EU), Japan, Canada, Switzerland, Great Britain, and Israel. In August 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) validated a marketing authorization (MAA) for ide-cel for the treatment of adult patients with RRMM who have received ≥3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy [Marketing Authorization Procedures: Review, Communication and Approval (Europe) (IDRAC 14888); EMA EPAR EMEA/H/C/004662 Revision 6: ABECMA (idecabtagene vicleucel), 27-July-2023 (IDRAC 368681)].
In January 2022, the Ministry of Health, Labour and Welfare (MHLW) in Japan approved ide-cel for the treatment of patients with RRMM who have received ≥3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody [Marketing Authorization Procedures: Review, Communication and Approval (Japan) (IDRAC 16686)]. In December 2023, the MHLW approved a supplemental application to add a new indication for ide-cel, which allowed for the treatment of patients who have received ≥2 prior lines of therapy.