Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up.
Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up.
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DOI：
10.1200/jco.22.00842
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发表时间：
2023-02-20
影响因子：
45.3
通讯作者：
Jagannath, Sundar
中科院分区：
文献类型：
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作者：
Martin, Thomas;Usmani, Saad Z.;Berdeja, Jesus G.;Agha, Mounzer;Cohen, Adam D.;Hari, Parameswaran;Avigan, David;Deol, Abhinav;Htut, Myo;Lesokhin, Alexander;Munshi, Nikhil C.;O'Donnell, Elizabeth;Stewart, A. Keith;Schecter, Jordan M.;Goldberg, Jenna D.;Jackson, Carolyn C.;Yeh, Tzu-Min;Banerjee, Arnob;Allred, Alicia;Zudaire, Enrique;Deraedt, William;Olyslager, Yunsi;Zhou, Changwei;Pacaud, Lida;Madduri, Deepu;Jakubowiak, Andrzej;Lin, Yi;Jagannath, Sundar
CARTITUDE-1是一项Ib/II期研究，评估了西拉他汀自体胶囊(Cilta-cel)在经过严格预处理的复发/难治性多发性骨髓瘤患者中的安全性和有效性，在12个月后产生了早期、深入和持久的反应。在这里，我们介绍了最后一位患者两年后的最新结果(中位随访[mfu]大约28个月)，包括对高危患者亚组的分析。符合条件的患者有复发/难治性多发性骨髓瘤，接受过≥3个既往治疗方案，或对蛋白酶体抑制剂和免疫调节药物双重耐药，曾接受蛋白酶体抑制剂、免疫调节药物和抗CD38治疗。患者在淋巴枯竭后5-7天接受单次小管输注。答复由一个独立审查委员会进行评估。平均随访27.7个月(N=97)，总有效率97.9%(95%CI，92.7~99.7)，82.5%(95%CI，73.4~89.4)达到完全缓解。中位反应持续时间是不可估量的。中位无进展生存期(PFS)和总生存期(OS)均未达到，27个月PFS和OS率分别为54.9%(95%CI，44.0~64.6)和70.4%(95%CI，60.1~78.6)。所有亚组的总体应答率都很高(95.1%-100%)。高危细胞遗传学、国际分期系统III期、高肿瘤负荷或浆细胞瘤患者的应答持续时间、PFS和/或OS较短。自上一次报告以来，安全性状况可控，没有新的毛囊相关细胞因子释放综合征和1例新的帕金森综合征病例(毛囊后第914天)。在大约28个月的MFU中，在标准亚组和高危亚组中观察到，使用西尔替赛治疗的患者保持了深刻和持久的反应。Cilta-cel的风险/收益状况仍然有利，并有更长的随访期。
CARTITUDE-1, a phase Ib/II study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma, yielded early, deep, and durable responses at 12 months. Here, we present updated results 2 years after last patient in (median follow-up [MFU] approximately 28 months), including analyses of high-risk patient subgroups. Eligible patients had relapsed/refractory multiple myeloma, had received ≥ 3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. Patients received a single cilta-cel infusion 5-7 days after lymphodepletion. Responses were assessed by an independent review committee. At a MFU of 27.7 months (N = 97), the overall response rate was 97.9% (95% CI, 92.7 to 99.7); 82.5% (95% CI, 73.4 to 89.4) of patients achieved a stringent complete response. Median duration of response was not estimable. Median progression-free survival (PFS) and overall survival (OS) were not reached; 27-month PFS and OS rates were 54.9% (95% CI, 44.0 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. Overall response rates were high across all subgroups (95.1%-100%). Duration of response, PFS, and/or OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas. The safety profile was manageable with no new cilta-cel–related cytokine release syndrome and one new case of parkinsonism (day 914 after cilta-cel) since the last report. At approximately 28 months MFU, patients treated with cilta-cel maintained deep and durable responses, observed in both standard and high-risk subgroups. The risk/benefit profile of cilta-cel remained favorable with longer follow-up.