Discussion
extramedullary disease, CRS, neurotoxicity, BOR, neurotoxic, Neurotoxicity
DISEASE PROGRESSION, EVENT, EVENTS
This sub-analysis of KarMMa is one of the first studies, along with the sub-analysis of CARTITUDE-1 [Based on the results from all patients in the KarMMa trial [Overall, the results observed in the Japanese cohort were consistent with the non-Japanese cohort, where the null hypothesis (≤ 10% of patients receiving ide-cel would have a BOR of CR/sCR) was rejected, although comparisons between the Japanese and non-Japanese cohorts should be interpreted with caution due to the small sample size for the Japanese cohort. A numerically higher ORR was observed in the Japanese population (89%) than in the non-Japanese population (73%) [The overall safety profile in the Japanese cohort was predictable, with early onset and resolution of CRS and neurotoxicity consistent with the non-Japanese population [Neurotoxicity after ide-cel infusion was infrequent in the Japanese cohort. Only 1 patient experienced grade 2 neurotoxicity, and this was well managed. Potential factors that could have triggered the neurotoxic event in this patient include grade 2 CRS prior to and overlapping with neurotoxicity, extramedullary disease experienced between screening and baseline, and possible rapid disease progression that occurred during bridging therapy with lenalidomide, carfilzomib, and dexamethasone. However, there does not appear to be an association of peak CAR T cell or lactate dehydrogenase levels with neurotoxicity in this patient as they did not have higher peak levels of CAR T cells or lactate dehydrogenase levels than patients who did not experience neurotoxicity. The rate of neurotoxicity in the Japanese cohort is consistent with the low rates of neurotoxicity seen in the non-Japanese cohort: 18% of the patients experienced any-grade neurotoxicity.The cellular kinetics findings were similar to previous reports from the non-Japanese patient population in the KarMMa trial [Across all KarMMa analyses, patients with RRMM treated with ide-cel showed deep and durable responses and superior responses compared with non-CAR T cell therapies [This study had several limitations. With only 9 patients in the Japanese cohort, the sample size was small, therefore comparisons must be made with caution. The study was also a single-arm, open-label study; therefore, no direct comparisons can be made to other therapies or populations.In this sub-analysis of the KarMMa study, Japanese patients treated with ide-cel had an ORR of 89% and a CR rate of 56%, with a median follow-up of 12.9 months. CRS and neurotoxicity events were well managed and resolved within a short period of time. These results support ide-cel as a treatment option for heavily pretreated Japanese patients with RRMM and suggest a favorable clinical benefit–risk profile.