Division of Hematology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
Int J Hematol. 2023 May;117(5):729-737. doi: 10.1007/s12185-023-03538-6. Epub 2023 Jan 24.
BACKGROUND: In the phase 2 KarMMa trial, patients with relapsed/refractory multiple myeloma (RRMM) achieved deep and durable responses with idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy. Here we report a sub-analysis of the Japanese cohort of KarMMa. METHODS: Adult patients with RRMM who had received ≥ 3 prior treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and had disease refractory to last treatment received ide-cel at a target dose of 450 × 10 CAR positive T cells. RESULTS: Nine patients were treated with ide-cel. The overall response rate was 89% (median follow-up, 12.9 months). The best overall response was stringent complete response in 5 patients (56%), very good partial response in 3 (33%), and stable disease in 1. Median duration of response was not reached. All patients experienced grade ≤ 2 cytokine release syndrome and one patient experienced grade 2 neurotoxicity, but all resolved. Two patients died, one each from plasma cell myeloma and general health deterioration. CONCLUSION: Ide-cel yielded deep, durable responses with a tolerable and predictable safety profile in Japanese patients with RRMM. These results are similar to those of the non-Japanese population in KarMMa.
背景:在 2 期 KarMMa 试验中,复发/难治性多发性骨髓瘤(RRMM)患者接受 B 细胞成熟抗原导向嵌合抗原受体(CAR)T 细胞疗法 idecabtagene vicleucel(ide-cel)治疗后,取得了深度和持久的缓解。在此,我们报告 KarMMa 日本队列的亚分析结果。
方法:接受过≥3 种先前治疗方案(包括蛋白酶体抑制剂、免疫调节剂和抗 CD38 抗体)治疗且对最后一次治疗耐药的 RRMM 成年患者,按目标剂量 450×106 CAR 阳性 T 细胞给予 ide-cel。
结果:9 例患者接受 ide-cel 治疗。总体缓解率为 89%(中位随访时间 12.9 个月)。最佳总体缓解为 5 例(56%)患者达到严格完全缓解,3 例(33%)患者达到非常好的部分缓解,1 例患者达到疾病稳定。缓解持续时间未达到中位数。所有患者均出现≤2 级细胞因子释放综合征,1 例患者出现 2 级神经毒性,但均得到缓解。2 例患者死亡,分别死于浆细胞瘤和一般健康状况恶化。
结论:ide-cel 在日本 RRMM 患者中具有深度和持久的缓解作用,且安全性可预测、耐受性良好。这些结果与 KarMMa 中的非日本人群相似。
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