CAR T-Cell Therapies for Multiple Myeloma Approved for Earlier Treatment
Of the six commercially available CAR T-cell therapies for treatment of hematologic malignancies, two therapies target the B-cell maturation antigen (BCMA) and are used for treatment of multiple myeloma: ciltacabtagen autoleucel or cilta-cel (CarvyktiÒ) and idecabtagene vicleucel or ide-cel (AbecmaÒ). In early April, FDA approved the supplemental Biologics License Applications (BLAs) submitted by Johnson & Johnson for cilta-cel and Bristol Myers Squibb for ide-cel that will allow treatment with these two CAR T-cell therapies earlier in the course of disease.
The treatment process for Car T-cell therapy requires patients to undergo a leukapheresis procedure to collect the patient’s T-cells. The leukapheresis product is then sent for manufacturing, where cells are genetically modified to express chimeric antigen receptors (CARs) on the cell surface. Cells are cultured and expanded to produce an adequate cell dose before cryopreservation and cell product transport back to the transplant center. The patient receives conditioning chemotherapy a few days prior to admission for infusion of the thawed CAR T-cell therapy product.
Prior to the approvals of the supplemental BLAs, cilta-cel and ide-cel were indicated for relapsed or refractory multiple myeloma after four or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Based on results of the Phase 3 KarMMa-3 clinical trial, the FDA approved the supplemental BLA for ide-cel, extending the indications to treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Based on the results of the CARTITUDE-4 clinical trial (NCT04181827), the FDA approved indications for cilta-cel have also been expanded. Cilta-cel is now approved for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. This approval makes cilta-cel the first BCMA-targeted therapy approved for treatment of multiple myeloma as early as first relapse.
References:
1. www.fda.gov - April 4, 2024 Approval Letter - ABECMA
2. www.fda.gov - April 5, 2024 Approval Letter - CARVYKTI
3. Bristol Myers Squibb press release - https://news.bms.com/news/details/2024/U.S.-FDA-Approves-Bristol-Myers-Squibb-and-2seventy-bios-Abecma-for-Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma-After-Two-Prior-Lines-of-Therapy/default.aspx
4. Johnson & Johnson press release - https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy