FDA Approves Abecma, a CAR-T Treatment, for Earlier Treatment of Multiple Myeloma

Abecma (idecabtagene vicleucel) is now approved to treat adults with relapsed and refractory multiple myeloma (R/R MM) after just two or more lines of therapy, including treatment with an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.

The approval is based on results from the phase 3 KarMMa-3 trial. In March 2024, the FDA Oncologic Drugs Advisory Committee (ODAC) voted 8-3 to recommend approval of Abecma based on the favorable benefit/risk profile for patients with triple-class exposed R/R MM. Although the FDA considers ODAC recommendations, it does not need to follow them.

The approval may signal the a new era of CAR-T treatment being used much earlier in the treatment of cancer instead of as a last resort. CAR-T involves genetically modifying the patient's T cells so T cells recognize and attack cancer. The treatments are currently priced so the cost runs into the hundreds of thousands of dollars.

“Abecma has demonstrated a progression-free survival benefit three times that of standard regimens in relapsed or refractory multiple myeloma, and we are now bringing the promise of cell therapy to patients earlier in their treatment journey,” Bryan Campbell, senior vice president, head of Commercial, Cell Therapy, Bristol Myers Squibb, said in a statement. “This approval underpins our commitment to addressing the unmet needs of more patients living with multiple myeloma by improving upon the current treatment paradigm, and we remain steadfast in our pursuit of innovation and advancing cell therapy research to deliver potentially transformative therapies.”

Abecma (pronounced uh-BEK-muh) is a B-cell maturation antigen (BCMA)–directed CAR T-cell therapy that already was first approved in March 2021 to treat adults with R/R MM after 4 or more lines of therapy. It was the first cell-based gene therapy approved to treat adults with MM.

KarMMa-3 is a phase 3, open-label, global, randomized controlled trial comparing Abecma with standard care in patients with R/R MM who received two to four prior lines of treatment. A total of 386 patients were enrolled in the study, with 254 randomly assigned to treatment with Abecma and 132 to standard care. Nearly all (94%) patients in the trial were refractory to prior treatment with Darzalex (daratumumab).

After a median follow-up of 15.9 months, Abecma had more than tripled progression-free survival (PFS) with a median PFS of 13.3 months compared with 4.4 months for standard care. Abecma reduced the risk of disease progression or death by 51%. In addition, 71% of patients on Abecma achieved a response compared with 42% on standard regimens. Only 5% on standard regimens achieved a complete response (CR) or stringent CR compared with 39% of patients on Abecma.

The median duration of response was 14.8 months on Abecma, but patients who achieved a CR or better had a median duration of response of 20 months.

From the KarMMa and KarMMa-3 studies, 89% of patients receiving Abecma experience any grade cytokine release syndrome with a median duration of 5 days. In addition, 40% of patients in the trials experienced any grade neurotoxicity, which had a median duration of 8 days.

“The results of the KarMMa-3 study are remarkable, especially given the historic outcomes with standard regimens for these patients with relapsed or refractory disease,” said Al-Ola A. Abdallah, M.D., clinical associate professor and clinical director, of Hematologic Malignancies and Cellular Therapeutics, University of Kansas, and chair of the U.S. Myeloma Innovations Research Collaborative. “With this approval, these patients now have an opportunity to be treated at an earlier line of therapy with a potentially transformative therapy that offers significantly improved progression-free survival for this difficult-to-treat disease that has had no established treatment approach.”