Sequencing novel agents in the treatment of classical Hodgkin lymphoma

ABSTRACT

Introduction

Classical Hodgkin lymphoma (cHL) is a curable disease, with durable remission achieved in about 80% of patients following first-line treatment. Three new drugs were introduced to the daily use in cHL: brentuximab vedotin (BV), nivolumab, and pembrolizumab. All three drugs were initially approved for the treatment of relapsed/refractory cHL (RRHL) and with their promising outcomes, they are now incorporated in different stages of the treatment.

Areas covered

We performed a literature search using PubMed on all cHL studies investigating BV and CPIs within the past 10 years. We analyzed literature to presume the sequencing of these novel agents.

Expert opinion

Addition of BV or nivolumab to AVD backbone in the frontline setting showed promising activity in advanced stage cHL. BV and CPIs combined with chemotherapy in the second-line treatment of cHL are evaluated in phase 2 studies and comparable results are reported. The results of BrECADD, with good efficacy and toxicity profile, should be followed. Pembrolizumab was shown to be more effective in RRHL compared to BV in patients who have relapsed post-ASCT or ineligible for ASCT. BV is used in post-ASCT maintenance in high-risk cases, although its role will be questioned as it is increasingly used in the frontline treatment.

KEYWORDS:

• Classical Hodgkin lymphoma
• brentuximab vedotin
• checkpoint inhibitor
• nivolumab
• pembrolizumab
• anti-PD1 antibody

Article highlights

• BV-AVD significantly improved PFS and OS in the front-line treatment of advanced stage cHL.

• However, BV-AVD has increased toxicity compared to ABVD, including neuropathy, febrile neutropenia, infections requiring prophylactic G-CSF use.

• Nivolumab-AVD is recently shown to be a candidate for new standard frontline therapy in advanced stage cHL. The benefit is more pronounced among patients over 60 years of age.

• BrECADD was associated with increased efficacy, decreased toxicity, and very good survival rates compared to eBEACOPP in the frontline treatment of advanced stage cHL.

• Combination of BV and CPI has demonstrated high response rate in RRHL and their combinations with chemotherapy increased their efficacy.

• Pembrolizumab, in comparison to BV, is the preferred treatment option for patients with RRHL who have relapsed post-ASCT or ineligible for ASCT.

Declaration of interest

B Ferhanoglu reports that they are a member of the Takeda Pharmaceuticals advisory board.

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

A peer reviewer on this manuscript has received research funding from SEAGEN, BMS and MERCK. A peer review on this manuscript has received honoraria for Seattle Genetics, Merck, and BMS, and research funding and consulting from Seattle Genetics and Merck.

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

Additional information

Funding

This paper was not funded.