Emerging Therapies in Relapsed and Refractory Hodgkin Lymphoma: What Comes Next After Brentuximab Vedotin and PD-1 Inhibition?

Purpose of review 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. Recent findings 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.