Division of Lymphoma-Myeloma, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Institute for Translational Research and Molecular Imaging, Catholic Institutes of Medical Science, Seoul, Korea.
Cancer Med. 2019 Nov;8(16):6860-6870. doi: 10.1002/cam4.2565. Epub 2019 Sep 27.
Ibrutinib is highly effective in patients with relapsed or refractory mantle cell lymphoma (MCL) in major clinical trials. Although there has been a dramatic improvement in survival outcomes in the salvage setting, nonresponders to ibrutinib have a bleak prognosis. Therefore, this retrospective study was conducted to identify the most appropriate therapeutic strategy and prognosis-related factors to predict the response of patients with relapsed or refractory MCL to ibrutinib monotherapy. Thirty-three consecutive refractory or relapsed MCL patients treated with ibrutinib were analyzed in this study. The median overall survival (OS) and progression-free survival (PFS) after initiation of ibrutinib were 35.1 months and 27.4 months, respectively. Risk factor analysis showed that high risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI) and nonresponse to ibrutinib at the first three cycles were significantly associated with inferior OS. Poor PFS was associated with high-risk biologic MIPI, prior bendamustine exposure, and nonresponse to ibrutinib during the first three cycles. After ibrutinib failure, primary nonresponders had poorer OS and PFS than inconsistent responders. The overall response rate for the first salvage therapy was only 33%, with a median TTP of 3.2 months. There was no effective therapeutic strategy except for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although ibrutinib responders exhibited favorable survival outcomes, nonresponders had a dismal prognosis. To overcome these limitations, it may be necessary to modify therapeutic strategies, such as selecting inconsistent responders for earlier allo-HSCT.
依鲁替尼在大型临床试验中对复发/难治性套细胞淋巴瘤(MCL)患者具有高度疗效。尽管在挽救性治疗中,患者的生存结果有了显著改善,但对依鲁替尼无反应的患者预后仍不容乐观。因此,本回顾性研究旨在确定最合适的治疗策略和预后相关因素,以预测复发/难治性 MCL 患者对依鲁替尼单药治疗的反应。本研究分析了 33 例连续接受依鲁替尼治疗的难治性或复发性 MCL 患者。依鲁替尼起始后患者的中位总生存期(OS)和无进展生存期(PFS)分别为 35.1 个月和 27.4 个月。风险因素分析显示,根据套细胞淋巴瘤国际预后指数(MIPI)的高危和依鲁替尼前三个周期无反应与较差的 OS 显著相关。不良的 PFS 与高风险的生物学 MIPI、既往苯达莫司汀暴露以及前三个周期依鲁替尼无反应相关。依鲁替尼失败后,原发性无反应者的 OS 和 PFS 较不一致反应者更差。首次挽救性治疗的总体缓解率仅为 33%,中位 TTP 为 3.2 个月。除异基因造血干细胞移植(allo-HSCT)外,尚无有效的治疗策略。尽管依鲁替尼应答者的生存结果良好,但无反应者的预后仍较差。为了克服这些局限性,可能需要修改治疗策略,例如选择不一致反应者进行更早的 allo-HSCT。