抗 PD-1 单抗卡瑞利珠单抗联合地西他滨治疗复发/难治性霍奇金淋巴瘤的随机 II 期研究中改善了临床结局。
Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma.
机构信息
Department of Bio-therapeutic, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
J Immunother Cancer. 2021 Apr;9(4). doi: 10.1136/jitc-2021-002347.
BACKGROUND
Programmed death-1 (PD-1) blockade monotherapy induced durable remission in a subset of patients with relapsed/refractory classical Hodgkin lymphoma (cHL). We asked whether the anti-PD-1 agent, camrelizumab, combined with the DNA demethylating agent, decitabine, improves progression-free survival (PFS) in patients with relapsed/refractory cHL over camrelizumab alone.
METHODS
This extended follow-up of an ongoing randomized phase II trial analyzed PFS among patients enrolled from January 2017 through July 2018. Sixty-one patients with relapsed/refractory cHL who were clinically naïve to PD-1 blockade and had received ≥2 previous therapies were randomized 1:2 to receive either camrelizumab (200 mg) monotherapy or camrelizumab (200 mg, day 8) combined with decitabine (10 mg/day, days 1-5) every 3 weeks.
RESULTS
With a median follow-up of 34.5 months, complete remission was 79% (95% CI 63% to 90%) in the decitabine-plus-camrelizumab group versus 32% (95% CI 13% to 57%) in the camrelizumab group (p=0.001). Median duration of response was not reached in the decitabine-plus-camrelizumab group, with an estimated 63% (95% CI 46% to 75%) of patients maintaining a response at 24 months. Median PFS with decitabine-plus-camrelizumab therapy was 35.0 months (95% CI not reached) and 15.5 months (95% CI 8.4 to 22.7 months) with camrelizumab monotherapy (HR, 0.46; 95% CI 0.21 to 1.01; p=0.02). Female gender, lower tumor burden, and fewer previous therapies were favorable prognostic factors for durable remission with camrelizumab monotherapy. The PFS benefits of decitabine-plus-camrelizumab versus camrelizumab were observed in most subgroups, especially in patients with relative larger tumor burdens and those treated with ≥3 prior therapies. After decitabine-plus-camrelizumab treatment, the percentage increase of circulating peripheral central memory T-cells correlated with both improved clinical response and PFS, suggesting a putative biomarker of decitabine-plus-camrelizumab therapy for cHL.
CONCLUSIONS
Decitabine-plus-camrelizumab results in longer PFS compared with camrelizumab alone in patients with relapsed/refractory cHL.
TRIAL REGISTRATION NUMBERS
NCT02961101 and NCT03250962.
背景
程序性死亡受体-1（PD-1）阻断单药治疗在一部分复发/难治性经典霍奇金淋巴瘤（cHL）患者中诱导了持久缓解。我们想知道抗 PD-1 药物卡瑞利珠单抗联合去甲基化药物地西他滨是否能改善复发/难治性 cHL 患者的无进展生存期（PFS），优于卡瑞利珠单抗单药治疗。
方法
这是一项正在进行的随机二期试验的扩展随访，分析了 2017 年 1 月至 2018 年 7 月期间入组的患者的 PFS。61 例复发/难治性 cHL 患者对 PD-1 阻断无临床经验，且接受过≥2 种先前治疗，按 1:2 随机分为卡瑞利珠单抗（200mg）单药治疗组或卡瑞利珠单抗（200mg，第 8 天）联合地西他滨（10mg/天，第 1-5 天）每 3 周治疗组。
结果
中位随访 34.5 个月时，地西他滨联合卡瑞利珠单抗组的完全缓解率为 79%（95%CI 63%至 90%），而卡瑞利珠单抗组为 32%（95%CI 13%至 57%）（p=0.001）。地西他滨联合卡瑞利珠单抗组的中位缓解持续时间未达到，估计 24 个月时 63%（95%CI 46%至 75%）的患者保持缓解。地西他滨联合卡瑞利珠单抗组的中位 PFS 为 35.0 个月（95%CI 未达到），卡瑞利珠单抗单药组为 15.5 个月（95%CI 8.4 至 22.7 个月）（HR，0.46；95%CI 0.21 至 1.01；p=0.02）。女性、较低的肿瘤负担和较少的先前治疗是卡瑞利珠单抗单药治疗持久缓解的有利预后因素。与卡瑞利珠单抗单药治疗相比，地西他滨联合卡瑞利珠单抗治疗在大多数亚组中均观察到 PFS 获益，尤其是在肿瘤负担相对较大和接受≥3 种先前治疗的患者中。在地西他滨联合卡瑞利珠单抗治疗后，外周循环中央记忆 T 细胞的百分比增加与临床反应改善和 PFS 相关，提示地西他滨联合卡瑞利珠单抗治疗 cHL 的潜在生物标志物。
结论
地西他滨联合卡瑞利珠单抗治疗复发/难治性 cHL 患者的 PFS 长于卡瑞利珠单抗单药治疗。
试验注册
NCT02961101 和 NCT03250962。
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