The overall outcome of patients with advanced-stage follicular lymphoma (FL) has improved significantly. However, some patients still develop multiple relapsed/refractory FL (RRFL). To address the still-limited data on this population, we performed this multi-center retrospective study. We analyzed 41 patients who received third-line treatment for RRFL at 8 institutes. The median age at diagnosis was 59 years (range, 38–70). The median progression-free survival (PFS) and probability of PFS at 2 years were 1.61 years and 39.4%, respectively, after third-line chemotherapy, and 0.45 years and 19.0%, respectively, after fourth-line chemotherapy. Objective response (OR) after third-line chemotherapy was achieved in 24 patients (53.7%). Bendamustine (Ben)-based regimens were associated with a significantly higher OR rate than other regimens (77.8% vs. 40.0%, respectively, P = 0.025). The median overall survival (OS) and probability of OS at 2 years were 4.71 years and 65.9%, respectively, after third-line chemotherapy, and 1.01 year and 45.1%, respectively, after fourth-line chemotherapy. In conclusion, this study had a small sample size and retrospective design, but it was able to demonstrate poor response rate and duration in patients with multiple RRFL, particularly after fourth-line chemotherapy. The optimal treatment strategy in this population should be clarified, including possibly hematopoietic stem cell transplantation.

晚期滤泡性淋巴瘤（FL）患者的总体预后明显改善。但是，一些患者仍会出现多发性复发/难治性FL（RRFL）。为了解决该人群仍然有限的数据，我们进行了这项多中心回顾性研究。我们分析了8家机构中接受RRFL三线治疗的41例患者。诊断时的中位年龄为59岁（范围38-70）。三线化疗后2年的中位无进展生存期（PFS）和PFS概率分别为三线化疗后的1.61年和39.4％，四线化疗后的分别为0.45年和19.0％。24例患者（53.7％）达到三线化疗后的客观反应（OR）。基于苯达莫司汀（Ben）的治疗方案的OR率明显高于其他治疗方案（77.8％vs.P  = 0.025）。三线化疗后2年的中位总生存（OS）和OS发生机率分别为三线化疗后的4.71年和65.9％，四线化疗后的分别为1.01年和45.1％。总之，该研究的样本量少且具有回顾性设计，但能够证明多发RRFL患者的反应率和持续时间较差，尤其是在四线化疗后。应该阐明该人群的最佳治疗策略，包括可能的造血干细胞移植。