Table_1_v1_Anti-Angiogenic Agent Combined with Anti-PD-1 Immunotherapy Showed Activity in Patients With Classical Hodgkin Lymphoma Who Have Failed Immunotherapy: A Retrospective Case Report Study.xlsx

BackgroundPD-1/PD-L1 inhibitor immunotherapy has showed impressive activity in various cancers, especially relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). However, acquired resistance is inevitable for most patients. Sometimes severe side effects also lead to treatment termination. When immunotherapy failed, alternative treatment options are limited. In the past few years, we have used the anti-angiogenic agent apatinib and PD-1 inhibitor camrelizumab to treat cHL patients who failed prior immunotherapy. In this study, we analyzed the data of these patients.
Patients and MethodsPatients with r/r cHL who had failed immunotherapy and subsequently received apatinib-camrelizumab (AC) combination therapy were included in this study. Patient data were collected from medical records and follow-up system. The efficacy and safety of AC therapy were analyzed.
ResultsSeven patients who failed immunotherapy were identified in our database, of which five patients acquired immunotherapy resistance and two patients experienced severe side effects. They received a combination of camrelizumab (200 mg every four weeks) and apatinib (425 mg or 250 mg per day). As of the cut-off date, these patients had received a median of 4 cycles (range, 2 - 31) of treatment. Two (2/7) patients achieved complete response, four (4/7) partial response, and one (1/7) stable disease. The median progression-free survival was 10.0 months (range, 2.0 – 27.8). Low-dose apatinib (250 mg) plus camrelizumab was well tolerated and had no unexpected side effects. Besides, no reactive cutaneous capillary endothelial proliferation was observed in AC-treated patients.
ConclusionsLow dose apatinib plus camrelizumab might be a promising treatment option for r/r cHL patients who have failed immunotherapy. This combination treatment is worthy of further investigation in more patients including solid cancer patients who have failed immunotherapy.

背景
PD-1/PD-L1抑制剂免疫治疗在多种恶性肿瘤中展现出显著临床活性，尤其针对复发/难治性（relapsed/refractory, r/r）经典型霍奇金淋巴瘤（classical Hodgkin lymphoma, cHL）。然而，多数患者不可避免地会出现获得性耐药，且部分严重不良反应可导致治疗终止。当免疫治疗失败后，可供选择的替代治疗方案十分有限。
近年来，我们团队采用抗血管生成药物阿帕替尼（apatinib）联合PD-1抑制剂卡瑞利珠单抗（camrelizumab），对既往免疫治疗失败的cHL患者开展治疗。本研究对该队列患者的临床数据进行了分析。

患者与方法
本研究纳入既往接受免疫治疗失败后，接受阿帕替尼-卡瑞利珠单抗（apatinib-camrelizumab, AC）联合治疗的r/r cHL患者。患者临床数据来源于病历档案及随访系统，旨在分析AC联合治疗方案的疗效与安全性。

结果
本研究数据库中共纳入7例免疫治疗失败的患者，其中5例出现免疫治疗获得性耐药，2例因严重不良反应终止治疗。所有患者均接受卡瑞利珠单抗（每4周200mg）联合阿帕替尼（每日425mg或250mg）治疗。截至数据截止日期，患者接受治疗的中位周期数为4周期（范围：2~31周期）。疗效评估显示，2例（2/7）达到完全缓解，4例（4/7）达到部分缓解，1例（1/7）为疾病稳定。中位无进展生存期为10.0个月（范围：2.0~27.8个月）。安全性方面，低剂量阿帕替尼（250mg）联合卡瑞利珠单抗耐受性良好，未出现预期外不良反应；且所有接受AC联合治疗的患者均未观察到反应性皮肤毛细血管内皮增生。

结论
低剂量阿帕替尼联合卡瑞利珠单抗或许可作为免疫治疗失败的r/r cHL患者的潜在治疗选择。该联合治疗方案值得在更多患者（包括免疫治疗失败的实体瘤患者）中开展进一步研究。