Introduction: Classic Hodgkin lymphoma (cHL) is a cancer of the immune system. Combination chemotherapy and radiation therapy result in high cure rate, nevertheless, up to a quarter of patients with advanced stage cHL may relapse. One mechanism of relapse is through immune evasion; cHL can avoid immune destruction by manipulating T cell regulatory protein programmed cell death-1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) interaction. Immune checkpoint inhibitors (CPIs), such as pembrolizumab are effective in relapsed/refractory (R/R) cHL.
Areas covered: We reviewed prior and ongoing investigation of pembrolizumab use in R/R cHL, maintenance after autologous stem cell transplant (ASCT) and in frontline setting. Phase I study of pembrolizumab (KEYNOTE-013) demonstrated safety in R/R cHL with subsequent phase II study (KEYNOTE-087) confirmed efficacy signal. Intriguing early data support the use of maintenance pembrolizumab after ASCT in high-risk cHL patients. Second line and frontline studies incorporating CPIs have demonstrated promising efficacy with no significant additive toxicities.
Expert opinion: Immune CPIs that block PD-1/PD-L1 and PD-L2 interaction are an effective strategy in R/R cHL. Pembrolizumab demonstrated safety and efficacy in the treatment of R/R cHL. The optimal utilization of pembrolizumab in frontline therapy is under investigation.
Keywords: Checkpoint inhibitors; PD-1; classic Hodgkin lymphoma; pembrolizumab.