Topline KarMMa-3 Results for Ide-Cel in Multiple Myleoma Show “Significant Improvement” in PFS

Topline results of the phase 3 KarMMa-3 trial for idecabtagene vicleucel (ide-cel), the chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma, met its primary end point of “significant improvement” in progression-free survival, according to Bristol Myers Squibb and 2seventy bio, which jointly announced the interim results.

The findings will be presented at an upcoming scientific meeting, the sponsors said in their statement.

Sold as Abecma, ide-cel received FDA approval in March 2021 on the strength of phase 2 findings that showed an overall response rate of 72% in 100 patients who were evaluated for efficacy. At the time of approval, ide-cell was the first FDA cell-based gene therapy for multiple myeloma.

KarMMa-3 (NCT03651128) is a randomized, global, multicenter, open-label study involving 381 patients with multiple myeloma who are relapsed and refractory after 2 to 4 lines of therapy and refractory to the last regimen. Investigators are evaluating ide-cel compared with standard combination regimens.

According to today’s statement, “Results of a pre-specified interim analysis conducted through an independent review committee showed that KarMMa-3 met its primary end point of demonstrating a statistically significant improvement in progression-free survival.” Treatment also showed improvement in a key secondary end point of ORR compared to standard regimens, while follow-up for overall survival is ongoing. Safety results were consistent with the prior results for ide-cel.

Ide-cel is a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, which uses the process of genetically modifying a patient’s T cells and infusing them back into the patient to attack the cancer. The current approval requires patients to have received 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody; however, ide-cel’s sponsors said the phase 3 results could lead to approval in earlier lines of treatment, which has occurred in the past year with other CAR T-cell therapies.

“Results from the KarMMa-3 study clearly demonstrate the clinical benefit of using a CAR T cell therapy earlier in the multiple myeloma treatment paradigm. These data reinforce our commitment to unlocking the full potential of cell therapy as we strive to build on the company’s heritage of innovation in blood cancers and transform patients’ lives through science," Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb, said in a statement.

“We are extremely pleased to have met the KarMMa-3 primary endpoint at an interim analysis. These results help to advance our efforts to make Abecma available for earlier lines of treatment for patients and we look forward to discussing these results with regulatory authorities,” Steve Bernstein, MD, chief medical officer, 2seventy bio, said in the statement.