Wang Chunmeng, Liu Yang, Dong Liang, Li Xiang, Yang Qingming, Brock Malcolm V, Mei Qian, Liu Jiejie, Chen Meixia, Shi Fengxia, Liu Miao, Nie Jing, Han Weidong
Department of Bio-therapeutic, The First Medical Centre in Chinese PLA General Hospital, Beijing, P.R. China.
Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
Clin Cancer Res. 2021 May 15;27(10):2782-2791. doi: 10.1158/1078-0432.CCR-21-0133. Epub 2021 Mar 5.
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.
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).
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.
Decitabine plus camrelizumab is associated with high response rates and long-term benefits in patients with relapsed/refractory cHL who failed PD-1 inhibitors.
程序性死亡受体1（PD-1）阻断单药疗法对复发/难治性经典型霍奇金淋巴瘤（cHL）有效，但有一部分患者对PD-1抑制剂耐药，只有少数患者能实现持久缓解。迫切需要针对单药抗PD-1治疗后复发/进展性cHL患者的有效治疗方案。抗PD-1与DNA去甲基化药物地西他滨联合用药在我们的测试队列中对抵抗抗PD-1的患者显示出了积极的初步结果。在此，我们评估地西他滨联合抗PD-1疗法在一个扩大队列以及更长随访期后的疗效。
我们呈现了复发/难治性cHL患者的缓解率和无进展生存率，这些患者在先前接受抗PD-1单药治疗后复发/进展，在一项II期试验（ClinicalTrials.gov：NCT02961101和NCT03250962）中每3周接受地西他滨（10毫克/天，第1 - 5天）联合抗PD-1卡瑞利珠单抗（200毫克，第8天）治疗。
总体而言，51例患者（测试队列：25例，扩大队列：26例）接受了治疗，50例接受了疗效评估。测试队列中的客观缓解率为52%[9例完全缓解（CR）；36%]，扩大队列中的客观缓解率为68%（6例CR；24%）。地西他滨联合卡瑞利珠单抗治疗的中位无进展生存期分别为20.0个月和21.6个月，显著长于先前抗PD-1单药治疗所达到的生存期。在24个月时达到CR的患者中，估计78%观察到了持久缓解。地西他滨联合卡瑞利珠单抗治疗后，循环外周中央记忆T细胞比例的增加与临床缓解和无进展生存期均直接相关。
地西他滨联合卡瑞利珠单抗对PD-1抑制剂治疗失败的复发/难治性cHL患者具有高缓解率和长期获益。
