FDA Accepts sBLA of Ide-cel for Triple-Class Exposed R/R Multiple Myeloma
Positive data from the phase 3 KarMMA-3 study has led to multiple regulatory applications being accepted for ide-cel as a treatment option for patients with relapsed/refractory multiple myeloma.
The FDA has accepted a supplemental biologics license application for idecabtagene vicleucel (ide-cel; Abecma) for the treatment of adult patients with relapsed and refractory (R/R) multiple myeloma who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.1
Ide-cel is a chimeric antigen receptor (CAR) T-cell therapy currently being evaluated in the KarMMa-3 study (NCT03651128). According to interim data from the study published in The New England Journal of Medicine, ide-cel significantly reduced the risk of disease progression or deathby 51% compared with standard regimens for the treatment of this patient population, and at a median follow-up of 18.6 months, patients treated with ide-cel had a median progression-free survival of 13.3 months vs 4.4 months with the standard-regimen (HR, 0.49; 95% CI, 0.38-0.65; P < .001).
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 16, 2023.
“Ide-cel in KarMMa-3 had demonstrated a significant progression-free survival benefit compared with standard of care options, respectively, making a case that ide-cel should be a preferred option over the standard of care regimens for this early, relapsed patient population,” Ajay Nooka, MD, a professor and the director of the Myeloma Program, Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta, Georgia, told Targeted OncologyTM.
In addition to the FDA acceptance, the European Medicines Agency (EMA) validated the Type II variation application for ide-cel from Bristol Myers Squibb’s, based on data from the KarMMa-3 trial. With this validation of the application, the submission of ide-cel is complete and investigators can begin procedure and scientific assessment. Japan's Ministry of Health, Labour and Welfare also accepted a supplemental new drug application for ide-cel based on the same findings.
“Our continued focus on bringing [ide-cel] into earlier lines of treatment demonstrates our commitment to increasing treatment options and improving outcomes for patients living with multiple myeloma,” said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb, in the press release. “This FDA acceptance marks another step forward in our mission by bringing us closer to offering this potentially transformative, one-time CAR T treatment option to more patients.”
In the phase 3, open-label, global, randomized, controlled KarMMa-3 trial in which these 3 regulatory applications were based on, ide-cel investigated in comparison with standard combination regimens. Patients were randomly 2:1 to receive ide-cel at a dose ranging from 150 × 106 to 450 × 106 CAR-positive T cells, or treatment with 1 of the 5 standard regimens.
The study enrolled patients aged 18 years and older with R/R multiple myeloma who received at least 2 but no more than 4 prior MM regimens, prior treatment with daratumumab (Darzalex), and a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles. Patients must have also achieved a response to at least 1 prior treatment regimen, had an ECOG performance status of 0-1, adequate vascular access for leukapheresis, and have recovered to grade 1 or baseline of any non-hematologic toxicities.2
The primary end point of the trial was PFS, and secondary end points were overall response, overall survival, event-free survival, minimal residual disease, complete response, duration of response (DOR), time to response, adverse events, quality-of-life, time to next anti myeloma treatment, PFS after next line therapy, and pharmacokinetics.
Excluding Black race (7% of the patients in the ide-cel group vs 14% of patients in the standard-regimen group), baseline characteristics among those enrolled were generally balanced between the 2 groups evaluated in the study. Of patients given ide-cel, 107 (42%) had high-risk cytogenetic abnormalities vs 61 (46%) in the standard-regimen group. In both groups, the median time since diagnosis was approximately 4 years, the median time to progression during the last previous anti myeloma therapy was approximately 7 months, and patients received a median number of 3 previous regimens (range, 2-4).3
Results from the KarMMa-3 study demonstrated that treatment with ide-cel led to a statistically significant and clinically meaningful improvement in PFS and overall response rate.
The intention-to-treat population included 29 patients in the ide-cel group and 6 patients in the standard-regimen group who did not receive the assigned therapy. Here, patients treated with ide-cel had a significantly longer PFS rate compared with patients given the standard-regimen. At 6 months the PFS was 73% in the ide-cel group vs 40% in the standard-regimen group, and at 12 months, PFS rates were 55% and 30%, respectively. The PFS benefit with ide-cel was consistent across prespecified subgroups.
Seventy-one percent of patients included in the ide-cel group and 42% of patients in the standard-regimen group had a response with treatment (P < .001). Additionally, 39% and 5%, respectively, achieved a complete response. Data on overall survival were immature at this point. Further, in the ide-cel arm, the median time to response was 2.9 months (range, 0.5-13.0) vs 2.1 months (range, 0.9-9.4) in the standard-regimen arm, and the median DOR was 14.8 months (95% CI, 12.0-18.6) vs 9.7 months (95% CI, 5.4-16.3).
Looking at safety, results were consistent with the well-established safety profile of ide-cel that was found in previous studies.
“Positive results from our phase 3 KarMMa-3 study demonstrate a significant clinical benefit of [ide-cel] across lines of care in triple-class exposed multiple myeloma,” said Steve Bernstein, MD, chief medical officer, 2seventy bio, in a press release1. “The acceptance of the sBLA brings us closer to expanding the benefits of [ide-cel] to myeloma patients earlier in their treatment course.”
