Programmed Cell Death-One Inhibition Therapy in Classical Hodgkin Lymphoma

The majority of patients with classical Hodgkin lymphoma (cHL) may be cured, but for patients with relapsed or refractory (R/R) cHL, the prognosis is unfavorable. Immune dysfunction is a significant contributor of relapse and a hallmark of cHL; in particular, the immune system is unable to eradicate lymphoma cells that overexpress immune checkpoint proteins. The blocking of this mechanism used by lymphoma cells to evade the immune system has resulted in clinical benefits. Use of checkpoint inhibitors (CPIs) in R/R cHL is associated with high response rates and an acceptable adverse effects profile. There is growing interest in combining chemotherapy with CPIs in frontline therapy of cHL treatment to improve relapse rates without significant additive toxicity. In this review, we discuss the current evidence supporting CPI use in R/R cHL and maintenance therapy. We present emerging CPI data in frontline adult cHL and assess its role in the elderly. In addition, we discuss critical immune-related toxicities and their management, and elaborate on the challenges of monitoring response and minimal residual disease as tools for maximizing efficacy by limiting toxicity.