Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop refractory disease or who become intolerant of BV and anti-PD-1 therapies (double refractory/intolerant; DR/INT). Here, we evaluated outcomes in patients with DR/INT cHL from 15 US academic medical centers. A total of 173 patients were identified as DR/INT. The median overall survival from the time of cHL diagnosis (OS-1) was 14.8 years (95% CI: 10.9–20.9 years) and the 10-year OS-1 estimate was 62% (95% CI: 52–70%). After accounting for differences in age, patients who underwent autologous stem cell transplant prior to developing DR/INT had significantly longer OS-1 (HR 0.53, 95% CI: 0.29–0.96, p = 0.04). Median OS from time of DR/INT (OS-2) was 7.4 years (95% CI: 4.3-NR) and the 5-year OS-2 estimate was 57% (95% CI: 48-66%). Both anti-PD-1 and BV based therapy rechallenge were effective with median PFS of 237 days (95% CI: 155-357 days) and 183 days (95% CI: 108–273 days), respectively. Finally, advanced therapy options such as CD30 directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after DR/INT were associated with improved OS-2 (p < 0.001). To our knowledge, this represents the largest cohort of patients with DR/INT cHL. OS-2 will serve as a benchmark for future studies aiming to improve survival in DR/INT cHL.
基于抗PD-1的疗法与本妥昔单抗（BV）显著改善了经典型霍奇金淋巴瘤（cHL）患者的生存状况，并已被纳入更前线的治疗方案。然而，对于发展为难治性疾病或无法耐受BV及抗PD-1治疗（双重难治/不耐受；DR/INT）患者的临床结局，目前数据尚不充分。本研究评估了来自美国15个学术医疗中心的DR/INT cHL患者的治疗结果。共确认173例患者为DR/INT。从cHL确诊时间起计算的中位总生存期（OS-1）为14.8年（95% CI：10.9–20.9年），10年OS-1估计值为62%（95% CI：52–70%）。校正年龄差异后，在发展为DR/INT前接受过自体造血干细胞移植的患者OS-1显著延长（HR 0.53，95% CI：0.29–0.96，p=0.04）。从DR/INT时间点起计算的中位总生存期（OS-2）为7.4年（95% CI：4.3-未达到），5年OS-2估计值为57%（95% CI：48-66%）。再次使用抗PD-1疗法和基于BV的治疗均显示疗效，中位无进展生存期分别为237天（95% CI：155-357天）和183天（95% CI：108–273天）。最后，在DR/INT后采用CD30靶向嵌合抗原受体T细胞疗法和异基因造血干细胞移植等前沿治疗手段与OS-2的改善相关（p<0.001）。据我们所知，这是目前最大规模的DR/INT cHL患者队列研究。OS-2数据将为未来旨在改善DR/INT cHL患者生存的研究提供基准参考。
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