Immune checkpoint inhibition in classical hodgkin lymphoma

ABSTRACT

Introduction: Hodgkin lymphoma (HL) accounts for 10% of lymphoma cases every year. HL is often curable by conventional chemotherapy and radiotherapy. However, in case of relapsed or refractory HL (r/r HL) after autologous hematopoietic stem cell transplantation (ASCT), few treatment options are currently available. Blockade of the immune checkpoint receptors, programmed death receptor-1 (PD-1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expressed on T-cells, and their ligands expressed on tumor-associated antigen-presenting cells (APCs), and Hodgkin and Reed/Sternberg (HRS) cells can remove inhibitory signals from anti-tumor T cells. Checkpoint blockade using monoclonal antibodies could be a potential treatment. Nivolumab and pembrolizumab are approved antibodies for the treatment of r/r HL.

Areas covered: This paper provides a comprehensive discussion of checkpoint inhibitors in HL treatment, including the most important clinical trials with mono- or combination therapies as a first or second-line treatment of HL.

Expert opinion: Relatively high response rates and an acceptable safety profile of checkpoint inhibitors make them an effective therapy for HL. The combination of checkpoint inhibition with other conventional cancer treatments and identifying the mechanisms responsible for resistance to checkpoint inhibition may improve the efficacy and safety of this immunotherapy, and enhance patient quality of life.

KEYWORDS:

• immunotherapy
• checkpoint inhibition
• Hodgkin lymphoma
• PD-1
• CTLA-4
• Nivolumab
• Pembrolizumab
• Ipilimumab

Article highlights

• There are few clinically available options for patients with relapsed/refractory Hodgkin lymphoma (r/r HL) after first-line treatment and failure of autologous hematopoietic stem cell therapy (ASCT).

• Immune checkpoint inhibition is novel cancer immunotherapy, which has shown promising response rates in many cancer types.

• Nivolumab and pembrolizumab are two checkpoint inhibitors that have been approved by FDA for r/r HL treatment.

• Ongoing studies are using immune checkpoint inhibitors plus chemotherapy, Brentuximab vedotin (BV) therapy, or other anti-cancer therapies as a second-line or first-line treatment in HL.

• The improved response rates with immune checkpoint inhibition monotherapy or combination therapy may be applicable in some eligible groups or all HL patients.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper received no funding.