Purpose: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. Patients and Methods: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1–14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1–3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1–21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). Results: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3–4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. Conclusions: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.

中文翻译：

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来那度胺加 R-GDP (R2-GDP) 治疗复发/难治性弥漫性大 B 细胞淋巴瘤：R2-GDP-GOTEL 试验和免疫生物标志物亚组分析的最终结果

目的：复发/难治性弥漫性大 B 细胞淋巴瘤 (R/R DLBCL) 需要新的治疗选择。基于来那度胺的治疗方案可以逆转利妥昔单抗治疗淋巴瘤的难治性。患者和方法：在 II 期 R2-GDP 试验中，78 名不适合自体干细胞移植的患者接受了以下治疗方案：来那度胺 10 mg 第 (D)1-14 天，利妥昔单抗 375 mg/m2 D1，顺铂 60 mg/ m2 D1，吉西他滨 750 mg/m2 D1 和 D8，以及地塞米松 20 mg D1-3，最多 6 个周期（诱导期），随后每 28 天 10 mg 来那度胺（或接受的最后一次来那度胺剂量）D1-21（维持期） ）。主要终点是总体缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）、安全性、关键循环免疫生物标志物的监测（欧盟临床试验注册号：EudraCT 2014-001620-29）。结果：中位随访 37 个月后，ORR 为 60.2% [完全缓解 (CR) 为 37.1%，部分缓解 (PR) 为 23.1%]。中位 OS 为 12 个月（CR 为 47 个月，无 CR 为 6 个月）；中位 PFS 为 9 个月（CR 为 34 个月 vs 无 CR 为 5 个月）。在原发性难治性人群中，ORR 为 45.5%（21.2% CR 和 24.3% PR）。最常见的3-4级不良事件是血小板减少症（60.2%）、中性粒细胞减少症（60.2%）、贫血（26.9%）、感染（15.3%）和发热性中性粒细胞减少症（14.1%）。完全反应与循环骨髓源性抑制细胞和调节性 T 细胞的急剧减少有关。结论：R2-GDP 方案在 R/R DLBCL（包括原发性难治性人群）中是可行的且高度活跃。