BMS and bluebird bio Receive FDA Priority Review for BCMA-Targeted CAR-T Therapy idecabtagene vicleucel in Relapsed/Refractory Multiple Myeloma

On September 22, Bristol-Myers Squibb (BMS) and bluebird bio jointly announced that the U.S. FDA had accepted their Biologics License Application for idecabtagene vicleucel (ide-cel), a BCMA-directed CAR-T cell immunotherapy, for the treatment of relapsed/refractory multiple myeloma (R/R MM), and had granted it Priority Review designation.

These patients had received at least three prior therapies, including immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. The FDA PDUFA date was March 27, 2021. Previously, ide-cel had received Breakthrough Therapy designation from the FDA and PRIME designation from the European Medicines Agency.

Multiple Myeloma (MM) is the second most common hematologic malignancy, after non-Hodgkin lymphoma. In recent years, despite significant advances in chemotherapy, proteasome inhibitors, immunomodulatory thalidomide derivatives, and CD38-targeted antibodies, nearly all patients eventually experience relapse. Therefore, there remains an urgent need for new therapeutic agents in this field.

BCMA is a transmembrane glycoprotein belonging to the tumor necrosis factor (TNF) receptor superfamily, also known as TNFRSF17 or CD269. As a critical B-cell biomarker widely expressed on the surface of multiple myeloma (MM) cells, BCMA has emerged as a prominent immunotherapeutic target for MM and other hematologic malignancies, becoming the second most popular target for anticancer cell therapies after CD19.

The New Drug R&D Monitoring Database (CPM) shows that, as of now, there are a total of 64 products targeting BCMA, with 21 CAR-T therapies under development. Among them, 6 products were developed by Chinese companies.

It should be noted that ide-cel had submitted a Biologics License Application (BLA) to the FDA in March this year. However, it was rejected by the FDA. According to the FDA's response at that time, the marketing application for ide-cel required additional data, including supplementary information on the Chemistry, Manufacturing, and Controls (CMC) module. This time, its BLA resubmitted in July has been accepted by the FDA and granted priority review status.

The regulatory application dossier for ide-cel is based on the results of the pivotal Phase II KarMMa study.

KarMMa Study

In this study, 128 heavily pre-treated patients with relapsed and refractory multiple myeloma, who had previously received at least three therapies and were refractory to the last therapy (defined by the International Myeloma Working Group [IMWG] as no response or disease progression within 60 days of treatment), received ide-cel at dose levels of 150–450 × 10⁶ CAR+ T cells. The median number of prior lines of therapy for these patients was six; 84% were triple-class refractory, meaning they were refractory to all three commonly used classes of agents, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 antibodies; 94% were refractory to anti-CD38 antibodies. The median follow-up time was 13.3 months.

The study met its primary endpoint of overall response rate (ORR) and the key secondary endpoint of complete response rate (CR). Safety results were consistent with previously reported data on ide-cel. The data showed an ORR of 73% across all dose levels, with 33% of patients achieving either complete response (CR) or stringent complete response (sCR). The median duration of response (DoR) was 10.7 months, and the median DoR for patients with CR or sCR was 19.0 months. The median progression-free survival (PFS) was 8.8 months, while the median PFS for patients with CR or sCR was 20.2 months. All patients who achieved CR or sCR and were evaluable for minimal residual disease (MRD) were MRD-negative. Consistent clinically meaningful benefits were observed across subgroups, with ORRs of 50% or higher in nearly all subgroups, including elderly and high-risk patients. Overall survival (OS) data continue to mature, with an estimated median OS of 19.4 months across all dose levels and a 12-month survival rate of 78%.