基于L-MIND研究（NCT02399085）的二期试验结果，抗CD19免疫治疗药物塔法西单抗与来那度胺联合应用于自体干细胞移植不合适的复发/难治性弥漫性大B细胞淋巴瘤（DLBCL）患者。我们报告了最终的五年分析结果。共80名患者（年龄≥18岁，1-3次系统治疗，ECOG PS为0-2）接受了持续12个周期的塔法西单抗和来那度胺联合治疗，然后转为单独应用塔法西单抗直至疾病进展（PD）或不能接受的毒性反应。主要终点是最佳客观缓解率（ORR）。次要终点包括缓解持续时间（DoR），无进展生存期（PFS），总生存期（OS）和安全性。探索性分析评估了前线治疗（pLoT）对疗效终点的影响。截至2022年11月14日的数据截止日期，ORR为57.5%，完全缓解（CR）为41.3%（n=33），与先前的分析结果一致。在中位随访时间为44.0个月时，中位DoR尚未达到。中位PFS为11.6个月[95% CI, 5.7-45.7]（中位随访时间为45.6个月），中位OS为33.5个月[95% CI, 18.3-NR]（中位随访时间为65.6个月）。一线治疗患者（n=40）的ORR较高（67.5%；CR为52.5%），而两线及以上治疗患者（n=40）的ORR为47.5%（CR为30%），但两个亚组中的中位DoR均尚未达到。其他探索性分析显示，各亚组之间的长期疗效结果保持一致。不良事件与先前报道的结果一致且可控，随着塔法西单抗单独治疗，其发生频率减少，没有新的安全问题。L-MIND的最终五年分析表明，这种免疫治疗组合耐受性良好，并具有持久的临床益处。

Tafasitamab, an anti-CD19 immunotherapy, is used with lenalidomide for patients with autologous stem cell transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) based on the results of the phase II L-MIND study (NCT02399085). We report the final 5-year analysis. Eighty patients (≥18 years, 1-3 prior systemic therapies, ECOG PS 0-2) received co-administered tafasitamab and lenalidomide for up to 12 cycles, followed by tafasitamab monotherapy until disease progression (PD) or unacceptable toxicity. Primary endpoint was best objective response rate (ORR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses evaluated efficacy endpoints by prior lines of therapy (pLoT). At data cut-off on November 14, 2022, ORR was 57.5%, with complete response (CR) of 41.3% (n=33), which was consistent with prior analyses. With median follow-up (mFU) of 44.0 months, median DoR was not reached. Median PFS was 11.6 months [95% CI, 5.7-45.7] (mFU 45.6), and median OS was 33.5 months [95% CI, 18.3-NR] (mFU 65.6). Patients with 1 pLoT (n=40) showed higher ORR (67.5%; 52.5% CR) compared with patients with ≥2 pLoT (n=40; 47.5%; 30% CR), but median DoR was not reached in either subgroup. Other exploratory analyses revealed consistent long-term efficacy results across subgroups. Adverse events were consistent with previous reports and manageable, and their frequency decreased during tafasitamab monotherapy, with no new safety concerns. This final 5-year analysis of L-MIND demonstrates that this immunotherapy combination is well tolerated and has long-term clinical benefit with durable responses.