Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.
Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.
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DOI：
10.1002/cnr2.1476
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发表时间：
2022-03
期刊：
影响因子：
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通讯作者：
Kyoto Clinical Hematology Study Group (KOTOSG) Investigators
中科院分区：
文献类型：
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作者：
Kawaji-Kanayama Y;Kobayashi T;Muramatsu A;Uchiyama H;Sasaki N;Uoshima N;Nakao M;Takahashi R;Shimura K;Kaneko H;Kiyota M;Wada K;Chinen Y;Hirakawa K;Fuchida SI;Shimazaki C;Matsumura-Kimoto Y;Mizutani S;Tsukamoto T;Shimura Y;Horiike S;Taniwaki M;Kuroda J;Kyoto Clinical Hematology Study Group (KOTOSG) Investigators
在关键临床试验中，卡非佐米（CFZ）（第二代蛋白酶体抑制剂）加地塞米松（DEX）联合或不联合来那度胺（LEN）的联合策略显示出对复发性/难治性多发性骨髓瘤（RRMM）患者的良好疗效。然而，他们对硼替佐米（BTZ）和/或LEN耐药的患者的影响尚未在日常实践中得到充分评估。为了评价基于CFZ治疗的真实的疗效和安全性;即CFZ联合LEN + DEX（KRD治疗）和CFZ联合DEX（KD治疗）在亚洲患者中的疗效和安全性，我们在京都临床血液学研究组进行了一项多中心前瞻性观察性研究。入组本研究的所有50例RRMM患者均在2017年至2019年期间接受了基于CFZ的治疗。KRD和KD分别给予31例和19例患者。KRD和KD的总有效率（ORR）分别为80.6%和73.7%。KRD的2年无进展生存期（PFS）和总生存期（OS）分别为58.5%和79.7%，KD为23.1%和52.6%。通过多变量分析，BTZ和LEN的难治性被确定为PFS和OS的独立不利因素。常见的非血液学AE包括高血压（42.0%）、发热（24.0%）、疲乏（24.0%）和感染（16.0%）。未观察到严重心力衰竭。本研究注册为UMIN 000025108。这项研究表明，需要开发新的含CFZ的策略，以克服BTZ和/或LEN的难治性，而KRD和KD在亚洲患者的日常实践中大多是可行的。
Combinatory strategies with carfilzomib (CFZ), a second‐generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting. To evaluate the real‐world efficacy and safety of CFZ‐based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group. All 50 patients with RRMM enrolled in this study were treated with CFZ‐based treatments between 2017 and 2019. KRD and KD were administered to 31 and 19 patients, respectively. The overall response rates (ORRs) were 80.6% with KRD and 73.7% with KD. Two‐year progression‐free survival (PFS) and overall survival (OS) were 58.5% and 79.7% with KRD, and 23.1% and 52.6% with KD. By multivariate analysis, refractoriness to BTZ and to LEN were identified as independent unfavorable factors for both PFS and OS. The common non‐hematologic AEs included hypertension (42.0%), fever (24.0%), fatigue (24.0%), and infection (16.0%). No serious heart failure was observed. This study is registered as UMIN000025108. This study suggests the need of the development of novel CFZ‐containing strategy which can overcome the refractoriness to BTZ and/or LEN, while both KRD and KD were shown to be mostly feasible in Asian patients in a daily practice setting.