Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Department of Hematology, Anqing Municipal Hospital, Anhui Medical University, Anqing, China.
Cancer Med. 2023 May;12(9):10553-10562. doi: 10.1002/cam4.5790. Epub 2023 Mar 13.
Approximately 40% patients of diffuse large B-cell lymphoma (DLBCL) would develop disease recurrence/progression after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single-drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti-tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long-term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R-CHOP treatment.
This retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6-8 cycles of R-CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n = 141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide, n = 50) and drug-free maintenance treatment (control, n = 91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression-free survival (PFS) was taken as the primary outcome.
Of the total 141 subjects, the median follow-up time was 30.9 months (range, 5.7-68.9 months). The 2-year PFS was 84% (95% CI: 74%-94%) in the lenalidomide group and 53% (95% CI: 43%-63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9 months (HR = 0.32; 95% CI: 0.16-0.63; p = 0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR = 0.42; 95% CI: 0.16-1.12; p = 0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1-2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3-4 adverse reaction.
Two-year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first-line R-CHOP treatment.
大约 40%的弥漫性大 B 细胞淋巴瘤（DLBCL）患者在接受一线 R-CHOP（利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松）诱导治疗后会出现疾病复发/进展，预后极差。延长这部分患者群体生存时间的有效策略是进行额外的单一药物维持治疗。来那度胺是一种具有口服活性的免疫调节药物，具有直接的抗肿瘤活性和间接的抗肿瘤作用，通过肿瘤微环境中的多种免疫细胞介导，如 B、T、自然杀伤（NK）和树突状细胞。结合其可控的毒性，它在长期维持治疗中很有前景。本研究旨在评估来那度胺维持治疗在接受 R-CHOP 治疗后获得完全缓解（CR）或部分缓解（PR）的 DLBCL 患者中的临床效果。
这项回顾性研究纳入了 2015 年 1 月 1 日至 2019 年 7 月 31 日期间接受 6-8 个周期 R-CHOP 治疗后获得 CR 或 PR 的 DLBCL 患者。患者（n=141）分别接受来那度胺维持治疗（来那度胺组，n=50）和无药物维持治疗（对照组，n=91）。来那度胺口服，每天 25mg，连用 10 天，每 21 天为一个周期，治疗疗程为 2 年。无进展生存期（PFS）为主要结局。
在总共 141 名患者中，中位随访时间为 30.9 个月（范围：5.7-68.9 个月）。来那度胺组 2 年 PFS 率为 84%（95%CI：74%-94%），对照组为 53%（95%CI：43%-63%）。来那度胺组中位 PFS未达到，对照组为 42.9 个月（HR=0.32；95%CI：0.16-0.63；p=0.001）。两组总生存期（OS）无显著差异（HR=0.42；95%CI：0.16-1.12；p=0.08）。对照组有 5 例（5.5%）患者发生中枢神经系统（CNS）复发，而接受来那度胺治疗的患者中无一例发生 CNS 复发。此外，中性粒细胞减少和皮肤反应是来那度胺治疗后最常见的 1-2 级不良事件，中性粒细胞减少是最常见的 3-4 级不良事件。
来那度胺维持治疗可显著延长接受一线 R-CHOP 治疗后获得 CR/PR 的 DLBCL 患者的 PFS。
