Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy
Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy
复制标题
地西他滨联合抗 PD-1 卡瑞利珠单抗对 PD-1 阻断单药治疗后进展或复发的霍奇金淋巴瘤患者的疗效
DOI：
10.1158/1078-0432.ccr-21-0133
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发表时间：
2021-05-15
影响因子：
11.5
通讯作者：
Han, Weidong
中科院分区：
文献类型：
--
作者：
Wang, Chunmeng;Liu, Yang;Han, Weidong
目的：程序性死亡-1（PD-1）阻断单药治疗对复发性/难治性经典霍奇金淋巴瘤（cHL）有效，但一部分患者对PD-1抑制剂无效，仅少数患者达到持久缓解。对于单药抗PD-1治疗后复发/进展的cHL患者，迫切需要有效的治疗方案。抗PD-1与DNA去甲基化剂地西他滨的组合在我们的测试队列中对抗PD-1耐药的患者中显示出阳性的初步结果。在这里，我们评估了地西他滨联合抗PD-1治疗在扩展队列和更长时间随访后的疗效。患者和方法：我们列出了既往抗PD-1单药治疗后复发/进展的复发/难治性cHL患者的缓解率和无进展生存率，这些患者在II期试验中每3周一次接受地西他滨（10 mg/天，第1-5天）联合抗PD-1 camrelizumab（200 mg，第8天）治疗（ClinicalTrials.gov：NCT 02961101和NCT 03250962）。结果：总体而言，51例患者（试验队列：25例，扩展队列：26例）接受了治疗，50例患者接受了疗效评价。试验组的客观缓解率为52%（9例完全缓解（CR）; 36%），扩展组为68%（6例CR; 24%）。地西他滨联合camrelizumab的中位无进展生存期分别为20.0和21.6个月，显著长于既往抗PD-1单药治疗的中位无进展生存期。在24个月时达到CR的患者中，估计有78%观察到持久缓解。在地西他滨加camrelizumab后，循环外周中枢记忆T细胞的比例增加与临床应答和无进展生存期直接相关。结论：对于PD-1抑制剂治疗失败的复发性/难治性cHL患者，地西他滨联合卡瑞珠单抗与高缓解率和长期获益相关。
Purpose: Programmed death-1 (PD-1) blockade monotherapy is effective in relapsed/refractory classical Hodgkin lymphoma (cHL), but a subset of patients is recalcitrant to PD-1 inhibitors and only a minority of patients achieves durable remission. Effective treatment regimens for those with relapsed/progressive cHL after single-agent anti-PD-1 are urgently needed. Anti-PD-1 combination with the DNA-demethylating agent decitabine showed positive preliminary results in our test cohort patients who were resistant to anti-PD-1. Here, we assess the efficacy of decitabine plus anti-PD-1 therapy in an expansion cohort and after longer follow-up. Patients and Methods: We present the response and progression-free survival rates from patients with relapsed/refractory cHL who relapsed/progressed after prior anti-PD-1 monotherapy, and who received decitabine (10 mg/day, days 1–5) plus the anti-PD-1 camrelizumab (200 mg, day 8), every 3 weeks in a phase II trial (ClinicalTrials.gov: NCT02961101 and NCT03250962). Results: Overall, 51 patients (test cohort: 25, expansion cohort: 26) were treated and 50 evaluated for efficacy. The objective response rate was 52% [nine complete responses (CR); 36%] in the test cohort, and 68% (six CRs; 24%) in the expansion cohort. Median progression-free survival with decitabine plus camrelizumab was 20.0 and 21.6 months, respectively, which was significantly longer than that achieved with prior anti-PD-1 monotherapy. Durable response was observed in an estimated 78% of patients who achieved CR at 24 months. After decitabine plus camrelizumab, the ratio increase of circulating peripheral central memory T cells directly correlated with both clinical response and progression-free survival. Conclusions: Decitabine plus camrelizumab is associated with high response rates and long-term benefits in patients with relapsed/refractory cHL who failed PD-1 inhibitors.