Ide-cel Produces PFS Benefit Vs Standard Regimens in Relapsed/Refractory Multiple Myeloma

Steve Bernstein, MD

The CAR T-cell therapy idecabtagene vicleucel (ide-cel; Abecma) elicited a statistically significant improvement in progression-free survival (PFS) vs standard combination regimens in patients with relapsed/refractory multiple myeloma who had received 2 to 4 lines of prior therapy, meeting the primary end point of the phase 3 KarMMA-3 trial (NCT03651128).¹

Along with an improvement in PFS, results from a prespecified interim analysis of the study showed that ide-cel demonstrated an improvement on overall response rate (ORR) compared with standard combination regimens, which was a key secondary end point. Follow-up for another secondary end point of overall survival (OS) is ongoing.

Investigators observed no new safety signals with the interim analysis. Results were consistent with the established safety profile for idecabtagene vicleucel from the phase 2 KarMMA trial (NCT03361748).

“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,” Anne Kerber, the senior vice president and head of Cell Therapy Development at Bristol Myers Squibb, stated in a news release. “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.”

In March 2021, the FDA approved ide-cel as the first BCMA-directed CAR T-cell therapy for patients with relapsed/refractory multiple myeloma after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, based on results from KarMMa. Ide-cel elicited an ORR of 72% (95% CI, 62%-81%) and a stringent complete response (sCR) rate of 28% (95% CI, 19%-38%) in an efficacy evaluable population (n = 100).²

The ongoing, global, multicenter, open-label KarMMA-3 study is the first randomized clinical trial to evaluate a CAR T-cell therapy in patients with multiple myeloma. Investigators enrolled adults with a documented diagnosis of multiple myeloma with measurable disease who received at least 2 prior lines of therapy but no more than 4 prior lines of therapy. Prior treatment needed to include daratumumab (Darzalex), a proteasome inhibitor, and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles.³ Patients needed to be refractory to their last treatment regimen.

Other key inclusion criteria included a response to at least 1 prior treatment regimen, an ECOG performance status of 0 or 1, recovery to grade 1 or baseline of any non-hematologic toxicities due to prior treatments (excluding alopecia and grade 2 peripheral neuropathy), and adequate vascular access for leukapheresis.

Key exclusion criteria included any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent them from participating; nonsecretory multiple myeloma; a history of malignancies, other than MM, unless the subject has been free of the disease for at least 5 years; known central nervous system involvement with multiple myeloma; or clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.

Upon enrollment, patients were randomly assigned to ide-cel or standard combination regimens that included daratumumab, pomalidomide (Pomalyst), dexamethasone, bortezomib (Velcade), ixazomib (Ninlaro), lenalidomide (Revlimid), carfilzomib (Kyprolis), or elotuzumab (Empliciti).

Along with ORR and OS, other secondary end points included event-free survival, minimal residual disease, complete response rate, duration of response, time to response, time to next treatment, second PFS, pharmacokinetics, patient-reported outcomes, and safety.

“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 [ide-cel] available for earlier lines of treatment for patients and we look forward to discussing these results with regulatory authorities,” Steve Bernstein, MD, the chief medical officer of 2seventy bio, stated in a news release. “[These] results are another important proof point for the transformative potential of autologous cell therapy and underscore the importance of continuing to study [ide-cel] in earlier treatment settings for multiple myeloma.”

References

1. Bristol Myers Squibb and 2seventy bio announce topline results from KarMMa-3 trial showing Abecma (idecabtagene vicleucel) significantly improves progression-free survival versus standard regimens in relapsed and refractory multiple myeloma. News release. Bristol Myers Squibb. August 10, 2022. Accessed August 10, 2022. https://bit.ly/3BVuvAI
2. U.S. Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the first anti-BCMA CAR T cell therapy for relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb and bluebird bio. March 26, 2021. Accessed August 10, 2022. https://bwnews.pr/39jWjjd
3. Efficacy and safety study of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM) (KarMMa-3). ClinicalTrials.gov. Updated August 2, 2022. Accessed August 10, 2022. https://clinicaltrials.gov/ct2/show/NCT03651128