Du Juan, Fang Baijun, Li Jian, Jin Jie, Wang Shunqing, Zou Dehui, Cai Zhen, Wang Hongxiang, Hu Jianda, Li Wei, Fu Chengcheng, Shao Zonghong, Xia Zhongjun, Liu Peng, Niu Ting, Tang En-Tzu, Kimball Amy S, Hou Jian, Chen Wenming
Department of Hematology, Shanghai Changzheng Hospital, Shanghai, China.
Department of Hematology, Henan Cancer Hospital, Zhengzhou, Henan, China.
Int J Hematol. 2021 Mar;113(3):422-429. doi: 10.1007/s12185-020-03044-z. Epub 2021 Jan 3.
The second-generation proteasome inhibitor carfilzomib produces superior outcomes in relapsed or refractory multiple myeloma (MM). We conducted a single-arm trial of twice-weekly carfilzomib (27 mg/m)-dexamethasone (Kd27) for relapsed and refractory MM in China. Kd27 was administered in 28-day cycles to 123 patients previously treated with ≥ 2 other regimens, including treatment with bortezomib and an immunomodulatory drug, and refractory to their most recent therapy. Overall response rate (ORR) was the primary endpoint; progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Primary analysis was conducted when all patients received ≥ 6 cycles of Kd27 or discontinued Kd27. Median age was 60 years; median number of prior regimens was 4; 74% were refractory to proteasome inhibitors and immunomodulatory drugs. ORR was 35.8% (95% CI 27.3-44.9), median PFS was 5.6 (95% CI 4.6-6.5) months, and median OS was 16.6 (95% CI 12.2-NE) months. Grade ≥ 3 adverse events (AEs) occurred in 76.4% of patients. Grade ≥ 3 AEs of interest included hypertension (13.8%), acute renal failure (3.3%), cardiac failure (0.8%), ischemic heart disease (0.0%), and peripheral neuropathy (0.0%); 5.7% of patients discontinued carfilzomib due to AEs. Carfilzomib-dexamethasone produced a clinically meaningful response without new safety findings in Chinese patients with previously treated MM.Trial registration: NCT03029234.
第二代蛋白酶体抑制剂卡非佐米在复发或难治性多发性骨髓瘤（MM）中产生了更好的疗效。我们在中国开展了一项针对复发和难治性MM的单臂试验，采用每周两次的卡非佐米（27mg/m）-地塞米松（Kd27）方案。Kd27以28天为一个周期，给予123例先前接受过≥2种其他方案治疗的患者，包括硼替佐米和免疫调节药物治疗，且对其最近一次治疗无效。总缓解率（ORR）是主要终点；无进展生存期（PFS）和总生存期（OS）是关键次要终点。当所有患者接受≥6个周期的Kd27或停用Kd27时进行初步分析。中位年龄为60岁；既往方案的中位数为4；74%的患者对蛋白酶体抑制剂和免疫调节药物耐药。ORR为35.8%（95%CI 27.3-44.9），中位PFS为5.6（95%CI 4.6-6.5）个月，中位OS为16.6（95%CI 12.2-NE）个月。76.4%的患者发生≥3级不良事件（AE）。≥3级感兴趣的AE包括高血压（13.8%）、急性肾衰竭（3.3%）、心力衰竭（0.8%）、缺血性心脏病（0.0%）和周围神经病变（0.0%）；5.7%的患者因AE停用卡非佐米。卡非佐米-地塞米松在先前接受治疗的中国MM患者中产生了具有临床意义的缓解，且无新的安全性发现。试验注册号：NCT03029234。
