An evaluation of pembrolizumab for classical Hodgkin lymphoma

ABSTRACT

Introduction

Pembrolizumab is an immune checkpoint inhibitor (ICI) targeted against the programmed death 1 (PD-1) pathway, a key pathway in the biology of Classical Hodgkin lymphoma (cHL). Anti-PD-1 antibodies are approved for use in relapsed/refractory cHL but ongoing studies continue to optimize the use of this treatment.

Areas Covered

This review highlights recent and established data regarding pembrolizumab in the management of relapsed/refractory cHL and emerging areas of study including translational biology, combinations with chemotherapy and trials earlier in the disease course

Expert Opinion

Pembrolizumab provides superior progression-free survival for patients with cHL who relapse post-autologous stem cell transplant or who have chemotherapy refractory disease and should be used in these high-risk populations. A key challenge remains the development of predictive biomarkers for anti-PD1 antibodies. There is promising evidence of the improved efficacy of salvage chemotherapy regimens and frontline regimens incorporating pembrolizumab but larger randomized studies are needed to demonstrate clear patient benefit.

KEYWORDS:

• Classical hodgkin’s lymphoma
• pembrolizumab
• autologous stem cell transplant
• immune checkpoint inhibitors
• lymphoma
• PD-1 inhibitors
• anti-PD-1 antibodies

Article highlights

• Signaling downstream of PD-1 results in immune effector inhibition which can be rescued using ICIs such as pembrolizumab

• Pembrolizumab has established efficacy as monotherapy in relapsed/refractory cHL with an overall response rate of approximately 70% and durable remissions although most patients do not achieve a complete remission

• KEYNOTE-204 is a phase 3 randomized study which showed an improved PFS of pembrolizumab when compared to brentuximab in patients with relapsed cHL, including those with high-risk features such as primary refractory disease or relapse within one year of treatment

• Studies looking at the combination of pembrolizumab with chemotherapy to optimize salvage regimens are underway with encouraging initial results

• Preliminary data incorporating pembrolizumab into the frontline setting for treatment of cHL is promising but larger cohorts and randomized data are needed

Declaration on Interest

RC Laister has received honoraria from AstraZeneca, Celgene, Janssen, Merck, Roche and Seattle Genetics; has consultancy or advisory roles with Protocol Intelligence; has received research grants or funding from AstraZeneca, Janssen and Roche.

J Kuruvilla has received honoraria from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Gilead Sciences, Janssen, Karyopharm Therapeutics, Incyte, Merck, Novartis, Roche, and Seattle Genetics; has consultancy or advisory roles with AbbVie, Bristol Myers Squibb, Gilead Sciences, Karyopharm Therapeutics, Medison Ventures, Merck, Roche/Genentech, and Seattle Genetics; has received research grants or funding from AstraZeneca, Janssen and Roche; and has membership on a DSMB for Karyopharm.

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 or other relationships to disclose.

Additional information

Funding

This paper was not funded.