Use of checkpoint inhibitors in patients with lymphoid malignancies receiving allogeneic cell transplantation: a review

Monoclonal antibodies against checkpoint receptors or its ligands have demonstrated high response rates and durable remissions in patients with relapsed Hodgkin lymphoma (HL) and other lymphoid malignancies. However, most patients will eventually progress on therapy and may benefit from further treatments including allogenic hematopoietic cell transplantation (allo-HCT). Furthermore, the use of checkpoint inhibitors (CPI) has emerged as a treatment option for patients relapsing after allo-HCT. The immune effects of the checkpoint blockade leading to a T-cell activation have raised some concerns on the safety of these therapies used either before or after allo-HCT, due to the potential risk of graft-versus-host disease (GVHD). Furthermore, CPI might also induce other immune toxicities, that can affect almost any organ, as a result of the dysregulation on the immune system balance. This review aims to focus on the evidence behind the use of CPI in patients with lymphoma who undergo allo-HCT. We summarize the clinical data generated to date about the use of CPI in HL and other lymphoid malignancies, the mechanisms of checkpoint inhibition in the context of allo-HCT as well as the clinical and biological observations of different GVHD prophylaxis in this setting. Furthermore, we discuss the evidence from retrospective series and early clinical trials on the feasibility and safety of the use of CPI in patients who relapsed after allo-HCT.