据我们所知，在复发或难治的经典霍奇金淋巴瘤患者中，这是第一个针对联合使用检查站抑制剂和传统化疗的临床试验，这些患者将接受自体干细胞移植。通过18F-氟脱氧葡萄糖-正电子发射断层扫描联合计算机断层扫描（FDG-PET/CT）评估复发或难治的经典霍奇金淋巴瘤患者接受挽救治疗后的完全缓解率。从2017年4月20日到2020年10月29日，美国的5个机构进行了单组、二期的非随机临床试验，以评估将Pembrolizumab添加到异环磷酰胺、卡铂和依托泊甙（ICE）化疗的疗效。这42名患者年龄在18岁及以上，Eastern Cooperative Oncology Group表现评分为0或1，并在接受了一线或两线化疗后经生物组织检查明确诊断为复发或难治的经典霍奇金淋巴瘤。患者需要具备移植的适当患者资质，且FDG-PET/CT检测到可测定的病灶。每21天给予两个疗程的Pembrolizumab（第1天静脉注射200毫克）与ICE化疗，随后进行干细胞移植和采集，然后进行一次Pembrolizumab单药治疗，并进行FDG-PET/CT反应评估。主要终点是由FDG-PET/CT检测到的完全缓解率，定义为Deauville评分为3或更低。完全缓解的患者进行自体干细胞移植。次要终点包括无进展生存、总生存、干细胞移植以及中性粒细胞和血小板成植。对不良事件进行监测，以评估安全性。共有42名患者入组，37名患者进行主要终点评估。患者的中位年龄为34岁（范围：19-70岁），女性患者25名（68％），非裔美国人6名（16％），白人患者26名（70％）。通过FDG-PET/CT成像评估37名患者的完全缓解率为86.5％（95％CI，71.2％至95.5％）;总体反应率为97.3％（36名患者），其中10.8％为部分反应（4名患者）。2名患者新出现FDG-PET阳性区域，经活检一个病例显示为非干酪性结节，另一个为反应性淋巴结。无进展生存和总生存2年的估计值分别为87.2％（32名患者；95％CI，77.3％至98.3％）和95.1％（95％CI，88.8％至100％）。将Pembrolizumab添加到ICE化疗不会对干细胞移植、采集或成植产生负面影响，与该患者群体和设置下的先前经验相似。结果表明，将Pembrolizumab添加到ICE化疗耐受性良好，且疗效显著，与仅化疗方案相比。支持在复发或难治的经典霍奇金淋巴瘤患者中进行进一步研究，这些患者适合进行自体干细胞移植。ClinicalTrials.gov识别号：NCT03077828。

To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant.To evaluate the complete response rate as assessed by 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma.A single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT.Two cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment.The primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety.Forty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting.Results suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant.ClinicalTrials.gov Identifier: NCT03077828.