Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

SIMPLE SUMMARY: The approach to relapsed and refractory classical Hodgkin lymphoma is rapidly evolving. Over the past five years, we have seen the arrival of novel immunotherapies with impressive clinical response rates. These agents are actively being investigated earlier in the sequence of therapies and in combination with other clinically active therapies. We are also witnessing the arrival of new therapies for multiply relapsed disease such as chimeric antigen receptor T-cell therapy, which holds immense promise for patients in the future. This review aims to provide an overview of recent updates to both the standard of care and investigational approaches for patients with relapsed and refractory classical Hodgkin lymphoma. ABSTRACT: Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.