利妥昔单抗联合克拉屈滨在惰性B细胞淋巴瘤患者中的疗效及安全性研究

Efficacy and safety of rituximab plus cladribine in patients with indolent B-cell lymphoma

目的:惰性非霍奇金淋巴瘤患者经多线治疗后对大剂量化疗的耐受性较差,最佳治疗方案仍有待探索。本研究旨在分析利妥昔单抗联合克拉屈滨(RC4)治疗初治和复发/难治性惰性B细胞非霍奇金淋巴瘤(B-NHL)的疗效及安全性。方法:回顾性分析2014年11月—2016年3月收治的19例使用RC4方案治疗的惰性B-NHL患者(2例华氏巨球蛋白血症,3例滤泡性淋巴瘤和14例边缘区B细胞淋巴瘤)的临床资料。RC4治疗方案为:在第1天使用375 mg/m2的利妥昔单抗,第25天使用克拉屈滨0.1 mg/(kg·d)。该方案每21 d重复一次,最多6个周期,评估该方案的疗效、不良事件和生存结果。结果:中位随访时间59.5个月(2465.6个月),19例惰性B-NHL患者中6例(31.6%)获得完全缓解,10例(52.6%)获得部分缓解,客观缓解率为84.2%(16/19)。19例患者的中位无进展生存期和总生存期均未达到,预估的5年无进展生存率和总生存率分别为83.1%和89.2%。17例初治患者的中位无进展生存期和总生存期也未达到。克拉屈滨的主要不良事件为血液学毒性和免疫抑制,一半以上(63.2%,12/19)的患者出现肺部感染,没有患者发生自身免疫性溶血。结论:本研究表明RC4治疗对于初治和复发/难治性惰性B-NHL是有效且可耐受的治疗方案。

Objective: Patients with indolent non-Hodgkin’s lymphoma usually require multi-line treatments and are less tolerant of high-dose chemotherapy. The best choice of treatment remains to be explored. In this study, we investigated the combination of rituximab and cladribine(RC4) therapy in the treatment of naive and relapse/refractory indolent B-cell non-Hodgkin’s lymphoma(B-NHL) patients. Methods: We retrospectively analyzed the clinical data of 19 patients with indolent B-NHL(2 cases of Waldenstrom’s macroglobulinemia, 3 cases of follicular lymphoma, and 14 cases of marginal zone B-cell lymphoma) treated between November 2014 and March 2016. RC4 treatment plan included rituximab 375 mg/m2 on day 1, and cladribine 0.1 mg/(kg·d) from day 2 to day 5. This plan was repeated every 21 days for a maximum of 6 cycles. We evaluated the treatment efficacy, adverse events and survival outcomes in the study. Results: The median follow-up time was 59.5 months(24 to 65.6 months). Among 19 patients with indolent B-NHL, 6 cases(31.6%) achieved complete response, 10 cases(52.6%) achieved partial response, and the objective response rate was 84.2%(16/19). The median progression-free survival(PFS) and overall survival(OS) were not reached, the estimated 5-year PFS rate and OS rate were 83.1% and 89.2% respectively. The median PFS and OS of 17 treatment-naive patients were also not reached. The main adverse events of cladribine were hematological toxicity and immunologic suppression. More than half of the patients(63.2%, 12/19) had pulmonary infection. There were no cases of autoimmune hemolysis. Conclusion: It suggests that RC4 treatment is an effective and well tolerated regimen in naive and relapse/refractory indolent B-NHL.