Mishima Yuko, Hashimoto Daigo, Ichii Michiko, Fukuhara Noriko, Uchida Toshiki, Kato Koji, Omi Ai, Koroki Yosuke, Shiga Kaname, Maruyama Dai
Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Ann Hematol. 2025 Sep 13. doi: 10.1007/s00277-025-06569-7.
Ibrutinib is a first-in-class oral inhibitor of Bruton's tyrosine kinase, which was investigated for the first-line treatment of mantle cell lymphoma (MCL) in the randomized, double-blind, phase 3 SHINE study. In SHINE, ibrutinib plus bendamustine and rituximab (BR) demonstrated superior progression-free survival (PFS) versus placebo plus BR in patients aged ≥ 65 years with previously untreated stage II-IV MCL. In this secondary efficacy analysis of SHINE, we assessed the correlation between best response and PFS (n = 523; 70% male; median age 71.0 years). After a median follow-up of 94.5 months, patients achieving complete response (CR) had longer median PFS in the ibrutinib (97.8 months) and placebo (87.9 months) arms than those with partial response (PR; 27.6 and 16.7 months, respectively) or progressive/stable disease (2.9 and 3.4 months, respectively). In the multivariate logistic regression analysis, patients receiving ibrutinib plus BR were more likely to achieve CR than those receiving placebo plus BR (odds ratio 1.48; 95% confidence interval 1.00-2.22). In conclusion, prolonged long-term PFS was more likely in patients with MCL who achieved CR following treatment with either ibrutinib plus BR or placebo plus BR, while CR was more likely in patients who had received ibrutinib plus BR. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) identifier 2012-004056-11 (registered 15 January 2013) WHO Universal Trial Number U1111-1137-0389.
依鲁替尼是一种一流的布鲁顿酪氨酸激酶口服抑制剂，在随机、双盲、3期SHINE研究中被用于套细胞淋巴瘤（MCL）的一线治疗。在SHINE研究中，对于年龄≥65岁、先前未经治疗的II-IV期MCL患者，依鲁替尼联合苯达莫司汀和利妥昔单抗（BR）对比安慰剂联合BR显示出更好的无进展生存期（PFS）。在SHINE的这项次要疗效分析中，我们评估了最佳缓解与PFS之间的相关性（n = 523；70%为男性；中位年龄71.0岁）。经过94.5个月的中位随访，在依鲁替尼组（97.8个月）和安慰剂组（87.9个月）中，达到完全缓解（CR）的患者的中位PFS长于部分缓解（PR）患者（分别为27.6个月和16.7个月）或疾病进展/稳定患者（分别为2.9个月和3.4个月）。在多因素逻辑回归分析中，接受依鲁替尼联合BR治疗的患者比接受安慰剂联合BR治疗的患者更有可能达到CR（比值比1.48；95%置信区间1.00 - 2.22）。总之，MCL患者在接受依鲁替尼联合BR或安慰剂联合BR治疗后达到CR的患者更有可能获得延长的长期PFS，而接受依鲁替尼联合BR治疗的患者更有可能达到CR。试验注册：欧盟临床试验注册（EudraCT）标识符2012 - 004056 - 11（2013年1月15日注册），世界卫生组织通用试验编号U1111 - 1137 - 0389。
