Division of Hematology, Department of Oncology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Front Immunol. 2024 Mar 6;15:1360275. doi: 10.3389/fimmu.2024.1360275. eCollection 2024.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting antibody-drug conjugate Brentuximab-Vedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable responses in relapsed/refractory (r/r) HL. However, patients with a history of allo-HSCT were frequently excluded from clinical trials due to concerns about the risk of graft-versus-host disease (GVHD). We report the clinical history of a patient with refractory classical HL who underwent two allo-HSCTs (first from matched unrelated and second from haploidentical donor) after relapsing on BV and nivolumab and for whom durable remission was finally obtained using BV-pembrolizumab combination for relapse after haploidentical HSCT. Such treatment was associated with the onset of GVHD after only two cycles which led to treatment discontinuation. However, the side effects were rapidly controlled, and after 2 years of follow-up, the patient is still in remission. Our data support the feasibility and efficacy of combining PD-1 blockade with BV to enhance the graft-versus-lymphoma effect after allo-HSCT.
异基因造血干细胞移植(allo-HSCT)是对高度化疗耐药性霍奇金淋巴瘤(HL)患者潜在的治愈性治疗选择。CD30 靶向抗体药物偶联物 Brentuximab-Vedotin(BV)和程序性死亡蛋白-1(PD-1)阻断剂在复发/难治性(r/r)HL 中具有临床活性,并获得了持久缓解。然而,由于对移植物抗宿主病(GVHD)风险的担忧,既往接受 allo-HSCT 的患者经常被排除在临床试验之外。我们报告了一名难治性经典 HL 患者的临床病史,该患者在接受 BV 和 nivolumab 治疗后复发,随后进行了两次 allo-HSCT(第一次来自匹配的无关供体,第二次来自单倍体相合供体),最后在单倍体相合 HSCT 后复发时使用 BV-pembrolizumab 联合治疗获得了持久缓解。这种治疗仅在两个周期后就引发了 GVHD,导致治疗中断。然而,副作用迅速得到控制,在 2 年的随访后,患者仍处于缓解期。我们的数据支持在 allo-HSCT 后联合 PD-1 阻断和 BV 以增强移植物抗淋巴瘤效应的可行性和疗效。