Relapsed and Refractory Classical Hodgkin Lymphoma: Keeping Pace With Novel Agents and New Options for Salvage Therapy

Abstract

The management of relapsed and refractory classic Hodgkin lymphoma (HL) has changed substantially since the approval of brentuximab vedotin (BV) and the checkpoint inhibitors nivolumab and pembrolizumab. For patients progressing after frontline treatment, second-line therapy followed by consolidation with autologous stem cell transplant (ASCT) remains the standard of care; however, although traditional combination chemotherapy regimens previously represented the only options for salvage, BV is now routinely incorporated into second-line therapy, and studies are evaluating checkpoint inhibitors in this setting as well. After ASCT, BV maintenance improves progression-free survival for patients at higher-risk, and studies are evaluating the role of post-ASCT maintenance with checkpoint inhibitors. Management of HL that progresses after ASCT remains a challenge. Although many patients achieve prolonged disease control with checkpoint inhibitors, the majority eventually progress and require additional therapy. Newer approaches, including CD30-directed chimeric antigen receptor–T-cell therapy, appear promising. Furthermore, allogeneic stem cell transplant remains an important consideration. Altogether, BV and checkpoint inhibitors have improved survival for patients with relapsed and refractory HL. However, the ideal place for these drugs in the treatment course of HL is still under investigation. Ongoing studies testing novel combinations and assessing for prognostic and predictive markers will ultimately define the optimal setting for these drugs in the treatment of relapsed and refractory HL.