Checkpoint Inhibition Therapy in Transplant-Ineligible Relapsed or Refractory Classic Hodgkin Lymphoma.

The checkpoint inhibitors nivolumab and pembrolizumab are principal treatment options for relapsed or refractory classic Hodgkin lymphoma. In patients who decline autologous stem-cell transplantation or who are unsuited for high-dose chemotherapy and subsequent autologous stem-cell transplantation because of comorbidities, the use of checkpoint inhibitors may improve overall survival and have a manageable side effect profile. This clinical review provides an evidence-based summary to guide practicing oncologists in the use of checkpoint inhibitors in relapsed or refractory classic Hodgkin lymphoma and includes checkpoint inhibitor efficacy and adverse effect profiles. We highlight the use of checkpoint inhibitors in the management of relapsed or refractory classic Hodgkin lymphoma in patients who are ineligible for an autologous stem-cell transplant with the goal of improving disease control while limiting adverse events.

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.

Pembrolizumab for the treatment of Hodgkin Lymphoma.

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.