Purpose: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. Results: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41–65) and 34% (95% CI, 24–46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 – 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. Conclusions: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

中文翻译：

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依鲁替尼和 R-GemOx 治疗复发或难治性非 GCB 型弥漫性大 B 细胞淋巴瘤患者：西班牙 GELTAMO 组的 II 期临床试验


目的：本 II 期临床试验评估了伊布替尼与利妥昔单抗、吉西他滨和奥沙利铂 (R-GemOx) 联合治疗非生发中心 B 细胞样 (non-GCB) 弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者的情况。患者和方法：IBDCL 试验 (NCT02692248) 包括组织学诊断为非 GCB DLBCL 且患有复发或难治性疾病的患者以及非干细胞移植候选者。患者接受诱导治疗，包括每两周一次标准剂量的 6 或 8 个周期的 R-GemOx，并结合依鲁替尼（每天 560 毫克），然后使用依鲁替尼维持治疗最长 2 年。主要目标是评估 4 个周期后的总体缓解率 (ORR)。结果：纳入 64 名患者，其中 72% 对最后一个方案耐药。第 4 个周期后的 ORR 和 CR 率分别为 53%（95% 置信区间 [CI]，41-65）和 34%（95% CI，24-46）。 24 名 (37%) 患者开始维持治疗，7 名 (11%) 患者完成了计划的 2 年。中位随访 29.7 个月（范围：0.4-48.6）后，估计的 2 年 PFS 和 OS 分别为 18% (95% CI, 8 – 28) 和 26% (95% CI, 14 - 37)，分别。最常见的≥3级治疗相关不良事件（TRAE）是血小板减少症（44%）、中性粒细胞减少症（30%）和贫血（14%）。分别有 6 名（9%）和 1 名（2%）患者报告了≥3 级感染性和心血管 TRAE。结论：伊布替尼联合 R-GemOx，然后进行伊布替尼维持治疗，在非 GCB DLBCL 患者中表现出令人鼓舞的抗肿瘤活性、持久的反应和可控的毒性。