Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Leukemia. 2021 Mar;35(3):777-786. doi: 10.1038/s41375-020-0939-1. Epub 2020 Jun 29.
Simultaneously targeting other pathways could increase the activity of PD-1 blockade in lymphoid malignancies not sensitive to single-agent blockade. We explored the safety and efficacy of combined PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory (R/R) lymphoid malignancies. This phase 1b trial enrolled adult patients with R/R classical Hodgkin lymphoma (cHL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM). Patients received nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri) until complete response (CR), progression, or unacceptable toxicity. The primary endpoint was safety and tolerability, while secondary endpoints included overall (ORR) and CR rates (CRR), progression-free and overall survival. Sixty-five patients were treated with nivo/ipi, and 72 with nivo/liri. Twenty-nine percent of patients experienced grade 3-4 treatment-related adverse events with nivo/ipi, and 15% with nivo/liri. In cHL, ORR was 74% for nivo/ipi and 76% for nivo/liri, CRRs were 23% and 24%, respectively. In B-NHL and T-NHL, ORR range was 9-22% and CRR was 0-6%. No patient with MM had an objective response. While both combinations were active in cHL, the toxicity of nivo/ipi was higher than expected from nivolumab alone. These data suggest no meaningful improvement in the efficacy of the combinations over single-agent nivolumab in the diseases studied.
同时针对其他途径可能会增加 PD-1 阻断在对单药阻断不敏感的淋巴恶性肿瘤中的活性。我们探索了 PD-1 和 CTLA-4 或 KIR 阻断联合治疗复发/难治性（R/R）淋巴恶性肿瘤患者的安全性和疗效。这项 1b 期试验纳入了 R/R 经典霍奇金淋巴瘤（cHL）、非霍奇金淋巴瘤（NHL）或多发性骨髓瘤（MM）的成年患者。患者接受纳武利尤单抗联合伊匹单抗（nivo/ipi）或利利鲁单抗（nivo/liri）治疗，直至完全缓解（CR）、进展或不可接受的毒性。主要终点是安全性和耐受性，次要终点包括总缓解率（ORR）和 CR 率（CRR）、无进展生存期和总生存期。65 例患者接受 nivo/ipi 治疗，72 例患者接受 nivo/liri 治疗。nivo/ipi 组有 29%的患者发生 3-4 级治疗相关不良事件，nivo/liri 组有 15%的患者发生。在 cHL 中，nivo/ipi 的 ORR 为 74%，nivo/liri 的 ORR 为 76%，CRR 分别为 23%和 24%。在 B-NHL 和 T-NHL 中，ORR 范围为 9-22%，CRR 为 0-6%。没有 MM 患者有客观缓解。虽然两种联合治疗在 cHL 中均有活性，但 nivo/ipi 的毒性高于单独使用纳武利尤单抗的预期。这些数据表明，在研究的疾病中，联合用药相对于单药纳武利尤单抗的疗效没有明显改善。
