曼特尔细胞淋巴瘤（MCL）是一种罕见的非霍奇金淋巴瘤，在漫长的时间里常常会出现化疗耐药性。伊布替尼和来那度胺具有独特的机制，因此有理由去探索与抗CD20免疫治疗的联合应用。在这项1b期研究中（NCT02446236），25名复发/难治性MCL患者接受了利妥昔单抗以及逐渐增加的来那度胺剂量（第1-21天）和28天循环中的560mg伊布替尼（第1-28天）。来那度胺的最大耐受剂量为20mg，最常见的≥3级不良事件是皮疹（32%）和中性粒细胞发热（24%）。最佳总有效率为88%，完全缓解率为83%，持续缓解时间（DOR）的中位数为36.92个月（95% CI 33.77, 51.37）。即使在难治性患者或具有高风险特征（如爆发变异、TP53突变、Ki-67 > 30%等）的情况下也观察到了反应。R2I对于复发/难治性MCL患者是安全且可耐受的。

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients (n = 25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1-21) and ibrutinib 560 mg (days 1-28) of 28-day cycles. The MTD for lenalidomide was 20 mg; most common grade ≥3 adverse events were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, CR rate was 83%, and median duration of response (DOR) was 36.92 months (95% CI 33.77, 51.37). Responses were seen even in refractory patients or with high-risk features (e.g. blastoid variant, TP53 mutation, Ki-67 > 30%). R2I was safe and tolerable in patients with R/R MCL.