Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) have poor outcomes compared with newly diagnosed, treatment-naïve patients. The phase 2, open-label DELPHINUS study evaluated daratumumab (16 mg/kg IV) plus backbone chemotherapy in children with relapsed/refractory B-cell ALL (n = 7) after ≥2 relapses, and children and young adults with T-cell ALL (children, n = 24; young adults, n = 5) or LL (n = 10) after first relapse. The primary end point was complete response (CR) in the B-cell ALL (end of cycle 2) and T-cell ALL (end of cycle 1) cohorts, after which patients could proceed off study to allogeneic hematopoietic stem cell transplant (HSCT). Seven patients with advanced B-cell ALL received daratumumab with no CRs achieved; this cohort was closed because of futility. For the childhood T-cell ALL, young adult T-cell ALL, and T-cell LL cohorts, the CR (end of cycle 1) rates were 41.7%, 60.0%, and 30.0%, respectively; overall response rates (any time point) were 83.3% (CR + CR with incomplete count recovery [CRi]), 80.0% (CR + CRi), and 50.0% (CR + partial response), respectively; minimal residual disease negativity (<0.01%) rates were 45.8%, 20.0%, and 50.0%, respectively; observed 24-month event-free survival rates were 36.1%, 20.0%, and 20.0%, respectively; observed 24-month overall survival rates were 41.3%, 25.0%, and 20.0%, respectively; and allogeneic HSCT rates were 75.0%, 60.0%, and 30.0%, respectively. No new safety concerns with daratumumab were observed. In conclusion, daratumumab was safely combined with backbone chemotherapy in children and young adults with T-cell ALL/LL and contributed to successful bridging to HSCT. This trial was registered at www.clinicaltrials.gov as NCT03384654.

中文翻译：

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Daratumumab 治疗儿科复发/难治性急性淋巴细胞白血病或淋巴细胞淋巴瘤：DELPHINUS 研究


与新诊断的初治患者相比，复发/难治性急性淋巴细胞白血病 （ALL） 或淋巴细胞淋巴瘤 （LL） 患者的预后较差。2 期、开放标签 DELPHINUS 研究评估了 daratumumab （16 mg/kg IV） 联合主干化疗在 ≥2 次复发后复发/难治性 B 细胞 ALL （n = 7） 儿童，以及首次复发后 T 细胞 ALL （儿童，n = 24;年轻人，n = 5） 或 LL （n = 10） 的儿童和年轻人。主要终点是 B 细胞 ALL （第 2 周期结束） 和 T 细胞 ALL （第 1 周期结束） 队列的完全缓解 （CR），之后患者可以继续进行同种异体造血干细胞移植 （HSCT）。7 例晚期 B 细胞 ALL 患者接受了 daratumumab 治疗，未达到 CR;这个队列因为徒劳而关闭。对于儿童 T 细胞 ALL、年轻成人 T 细胞 ALL 和 T 细胞 LL 队列，CR （第 1 周期结束） 率分别为 41.7% 、 60.0% 和 30.0% ;总体缓解率 （任何时间点） 分别为 83.3% （CR + CR 伴不完全计数恢复 [CRi]）、80.0% （CR + CRi） 和 50.0% （CR + 部分缓解）;微小残留病阴性率 （<0.01%） 分别为 45.8% 、 20.0% 和 50.0%;观察到的 24 个月无事件生存率分别为 36.1% 、 20.0% 和 20.0% ;观察到的 24 个月总生存率分别为 41.3% 、 25.0% 和 20.0%;同种异体 HSCT 率分别为 75.0% 、 60.0% 和 30.0%。未观察到 daratumumab 的新安全性问题。总之，daratumumab 与主干化疗安全地联合用于患有 T 细胞 ALL/LL 的儿童和年轻人，并有助于成功桥接至 HSCT。该试验在 www.clinicaltrials.gov 注册为 NCT03384654。