Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.
Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplant, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA.
Curr Hematol Malig Rep. 2021 Feb;16(1):1-7. doi: 10.1007/s11899-020-00603-3. Epub 2021 Jan 6.
The standard of care for relapsed/refractory (r/r) Hodgkin lymphoma (HL) patients is autologous stem cell transplantation (ASCT) for patients in a first or second relapse. However, a significant number of patients with r/r HL are either medically ineligible for ASCT or relapse post-ASCT. In recent years, significant advances have been made in the management of r/r HL with the introduction of the anti-CD30 antibody-drug conjugate (ADC) brentuximab vedotin (BV) and the anti-PD1 checkpoint inhibitors (CPI) nivolumab and pembrolizumab. Nonetheless, despite excellent tolerability and high response rates, the large majority of patients will ultimately progress on these agents. Allogeneic hematopoietic cell transplantation (alloHCT) has offered a potentially curative option for these patients, but high rates of morbidity and mortality have limited its application, and disease relapse is also common post-alloHCT. Thus, effective therapy for HL patients who fail BV and CPI therapy remains an unmet need. This review will cover different treatment strategies for HL patients in this setting with a focus on emerging new therapies.
Investigators have explored methods with the potential to restore sensitivity to BV and CPIs in patients who develop resistance. Additionally, promising new therapeutics are emerging, such as CD25-directed ADC therapy and CD30-directed chimeric antigen receptor (CAR) T cells. While no consensus guidelines exist for the management of HL patients refractory to BV and checkpoint blockade, potential novel strategies and therapeutics are currently under investigation in hopes of expanding the treatment landscape for this challenging patient population.
目的综述：对于首次或第二次复发的患者，自体干细胞移植（ASCT）是复发/难治性（r/r）霍奇金淋巴瘤（HL）患者的标准治疗方法。然而，仍有相当一部分 r/r HL 患者因医学原因不适合进行 ASCT 或在 ASCT 后复发。近年来，随着抗 CD30 抗体药物偶联物（ADC） Brentuximab vedotin（BV）和抗 PD1 检查点抑制剂（CPI）nivolumab 和 pembrolizumab 的引入，r/r HL 的治疗取得了重大进展。尽管这些药物具有良好的耐受性和高缓解率，但绝大多数患者最终仍会进展。异基因造血细胞移植（alloHCT）为这些患者提供了一种潜在的治愈选择，但发病率和死亡率高限制了其应用，移植后疾病也会复发。因此，对于接受 BV 和 CPI 治疗后失败的 HL 患者，仍需要有效的治疗方法。本综述将讨论这一背景下 HL 患者的不同治疗策略，重点关注新兴的新疗法。
最新发现：研究人员探索了在发生耐药的患者中恢复对 BV 和 CPIs 敏感性的潜在方法。此外，还出现了有前途的新疗法，如 CD25 靶向 ADC 疗法和 CD30 靶向嵌合抗原受体（CAR）T 细胞。尽管对于对 BV 和检查点阻断耐药的 HL 患者尚无共识指南，但目前正在研究潜在的新策略和疗法，希望能为这一具有挑战性的患者群体扩大治疗范围。
