BCMA-directed CAR-T still shows deep, durable response in heavily pretreated myeloma
Long-term results from the KarMMa trial continued to yield frequent deep and durable responses with idecabtagene vicleucel, a BCMA-directed CAR T-cell therapy, in heavily pretreated patients with relapsed or refractory multiple myeloma.
Based on early results from KarMMa, idecabtagene vicleucel (ide-cel; Abecma; Bristol Myers Squibb, bluebird bio) the FDA granted approval for use in patients with relapsed/refractory multiple myeloma after at least four prior lines of therapy.
“The objective of this analysis was to present longer term efficacy and safety results in patients treated with ide-cel in the KarMMa trial overall and by a number of prior lines of therapy, three vs. four or more,” Larry D. Anderson Jr., MD, PhD, associate professor at UT Southwestern Medical Center, said during his presentation at the virtual ASCO Annual Meeting, “since the FDA label is requiring at least four prior lines, and this study only required three.”
Relapsed or refractory patients received CAR-T after 3 days of lymphodepletion. Researchers examined ORR as the primary endpoint as well as complete response rate, PFS, OS and safety.
Of 140 patients in KarMMa, 128 received ide-cel (median follow-up, 15.4 months; median patient age, 61 years; median prior regimens, 6; triple-class refractory, 84%; penta-class refractory, 26%). Also, 88% of patients had bridging therapy.
The results revealed an ORR of 73% and a median PFS of 8.8 months in patients who received ide-cel, but both increased with higher dose. The ORR was 81% and the complete response rate was 39% at the highest target dose (450 × 106 CAR+ T cells), with the median PFS increasing to 12.2 months with longer follow-up. The 15-month event-free rate for OS was 71%, but OS continues to mature, and the median has not been reached yet, according to the abstract.
Cytopenias (97%) and cytokine release syndrome (CRS; 84%) were the most common toxicities and most CRS were low-grade, but five patients had grade 3, one had grade 4 (at 300 × 106) and one had grade 5 (at 300 × 106). Researchers reported neurotoxicity in 23 patients. Anderson said that the safety profile of ide-cel remained consistent with longer follow up, had similar rates of infections and second primary malignancies, with no observed unexpected gene therapy-related toxicities.
“The favorable benefit risk profile of ide-cel, regardless of the number of prior lines of therapy, supports its role as a treatment option for heavily pretreated relapse or refractory multiple myeloma,” Anderson concluded.
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Anderson Jr. LD, et al. Abstract 8016. Presented at: ASCO Annual Meeting; June 4-8, 2021 (virtual meeting).