Pembrolizumab for the treatment of Hodgkin Lymphoma

ABSTRACT

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
• classic Hodgkin lymphoma
• PD-1
• pembrolizumab

Box 1. Drug summary box

Table

Article highlights

• Pembrolizumab is an effective treatment option in patients with relapsed/refractory classic Hodgkin’s lymphoma.

• The use of pembrolizumab in frontline setting is under investigation.

• KEYNOTE-204 showed superior efficacy of pembrolizumab compared to brentuximab vedotin when used as salvage therapy in relapsed/refractory classic Hodgkin’s lymphoma.

• Immune related adverse events can occur with the use of pembrolizumab and patients should be monitored for development of such events.

• Future investigation will help to establish the potential role of pembrolizumab in patients with newly diagnosed classic Hodgkin’s lymphoma as part of combination multimodality treatment.

Declaration of interest

S Al Hadidi received a T32 training grant supported by Supported by National Heart, Lung, and Blood Institute grant No. 5T32HL092332-18. HJ Lee received research funding from Bristol Myer Squibb, Seattle Genetics, Oncternal Therapeutics, Takeda Pharmaceutical and Janssen Pharmaceutica. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.