Synchronizing the use of allogeneic hematopoietic cell transplantation in checkpoint blockade therapy for Hodgkin lymphoma

ABSTRACT

Introduction

The use of checkpoint blockade therapy (CBT) has shown impressive results for the treatment of relapsed/refractory Hodgkin lymphoma (cHL). The impact of CBT depends on the reversal of an exhausted T-cell immune phenotype and a consequential increase in the immunological, anti-tumor effect derived from a patient’s adaptive immunity. As most patients with classical Hodgkin lymphoma will relapse during or after this treatment, clinicians often provide consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in fit patients. However, the mechanisms responsible for CBT efficacy can also be those that increase the risk of immunological complications after alloHCT.

Areas covered

We carried out in-depth research on the current medical literature to report and discuss the mechanism of action of CBT within a cHL setting; clinical results of CBT in cHL setting pre-alloHCT and post-alloHCT; interactions between CBT and alloHCT; and further clinical considerations.

Expert opinion

Checkpoint blockade therapy is an effective strategy for relapsed/refractory cHL. Its use is associated with higher immunological toxicities when administered before or after alloHCT. Whenever alloHCT is planned, clinicians should follow international recommendations such as using post-transplant cyclophosphamide GVHD prophylaxis.

KEYWORDS:

• Allogeneic hematopoietic cell transplant
• classical Hodgkin lymphoma
• checkpoint blockade therapy
• PD-1 inhibitors

Article highlights

• Checkpoint inhibitors represent a novel cornerstone in therapy for Hodgkin lymphoma.

• Despite efficacy of these inhibitors, safety profile concerns should be established if used before or after allogeneic hematopoietic cell transplantation

• Initial studies reported a higher risk of hyperacute GVHD, veno-occlusive disease and non-infectious febrile syndrome.

• Administering post-transplant cyclophosphamide as GVHD prophylaxis showed potential to abrogate immunological side effects.

• A lower relapse rate was observed whenever checkpoint inhibitors were used before an allogeneic hematopoietic cell transplantation.

Acknowledgments

The authors would like to thank all patients and their families. The authors would also like to thank the CERCA program/Generalitat de Catalunya for institutional support.

Declaration of interest

A Mussetti disclosed research grants from Gilead and honoraria from Takeda and Novartis. A Sureda disclosed honoraria from Takeda, Celgene, Janssen, Gilead and Novartis. 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. 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 did not receive funding.