Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma
Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma
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抗 PD-1 抗体卡瑞利珠单抗联合低剂量地西他滨治疗复发/难治性经典霍奇金淋巴瘤
DOI：
10.1200/jco.18.02151
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发表时间：
2019-06-10
影响因子：
45.3
通讯作者：
Han, Weidong
中科院分区：
文献类型：
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作者：
Nie, Jing;Wang, Chunmeng;Han, Weidong
抗程序性死亡-1（PD-1）单药治疗复发/难治性经典型霍奇金淋巴瘤（cHL）患者有较高的缓解率，但很少观察到完全缓解（CR）。由于地西他滨是已知的，以提高T细胞功能，我们评估了安全性和有效性的抗PD-1 camrelizumab单独与地西他滨引发camrelizumab在复发性/难治性cHL.METHODS的患者，这两个手臂，开放标签，II期研究招募复发性/难治性cHL谁接受了至少两行以前的治疗。抗PD-1初治患者被随机分配（1：2）接受camrelizumab（200 mg）单药治疗或地西他滨（10 mg/d，第1 - 5天）+camrelizumab（200 mg，第8天）联合治疗，每3周一次。既往接受过抗PD-1治疗的患者被分配接受联合治疗。主要终点是CR率和safety. ResultsOverall，86例患者入组并进行反应评价，中位随访时间为14.9个月。在抗PD-1初治患者中，camrelizumab单药治疗的CR率为32%（19例患者中的6例），而地西他滨联合camrelizumab治疗的CR率为71%（42例患者中的30例）（P = 0.003）。在分析时，camrelizumab单药治疗6个月时的缓解持续率为76%，而地西他滨+camrelizumab为100%。对于既往接受过抗PD-1治疗的患者，地西他滨联合camrelizumab治疗后，28%达到CR，24%达到部分缓解。10例患者在6个月以上保持缓解，估计81%的缓解者在1年以上保持缓解。对于这两种治疗，最常见的不良事件是临床无关紧要的樱桃状血管瘤和白细胞减少症，是self-limited.CONCLUSION复发性/难治性cHL患者的CR率在临床上是幼稚的PD-1封锁是显着高于地西他滨加camrelizumab单用camrelizumab。地西他滨联合camrelizumab可逆转复发性/难治性cHL患者对PD-1抑制剂的耐药性。(C)2019年美国临床肿瘤学会
PURPOSE Anti-programmed death-1 (PD-1) monotherapy induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but complete remission (CR) is infrequently observed. As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti-PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL.METHODS This two-arm, open-label, phase II study enrolled patients with relapsed/refractory cHL who had received at least two lines of previous therapy. Anti-PD-1 treatment-naive patients were randomly assigned (1:2) to camrelizumab (200 mg) monotherapy or decitabine (10 mg/d, days 1 to 5) plus camrelizumab (200 mg, day 8) combination therapy every 3 weeks. Patients who were previously treated with anti-PD-1 were assigned combination therapy. Primary end point was CR rate and safety.RESULTS Overall, 86 patients were enrolled and evaluated for response, with a median follow-up of 14.9 months. In anti-PD-1-naive patients, CR rate was 32% (six of 19 patients) with camrelizumab monotherapy versus 71% (30 of 42 patients) who were administered decitabine plus camrelizumab (P = .003). At the time of analysis, the response duration rate at 6 months was 76% on camrelizumab monotherapy versus 100% on decitabine plus camrelizumab. For patients who were previously treated with anti-PD-1, 28% achieved CR and 24% partial response after decitabine plus camrelizumab. Ten patients maintained a response at more than 6 months and 81% of responders were estimated to have a response at more than 1 year. For both treatments, the most common adverse events were clinically inconsequential cherry hemangiomas and leukocytopenia that were self-limiting.CONCLUSION CR rate in patients with relapsed/refractory cHL who were clinically naive to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone. Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL. (C) 2019 by American Society of Clinical Oncology