Abstract The immune system plays a major role in preventing infections and cancers. Impairment in immunity may facilitate the development of neoplasia owing to defective immune surveillance, among other mechanisms. Immune evasion plays a significant role in relapse after allogeneic hematopoietic cell transplantation (alloHCT); one purported mechanism is through immune checkpoint signaling pathways. Checkpoint inhibitors (CPIs) are FDA approved for relapsed classical Hodgkin’s Lymphoma (cHL), primary mediastinal large B cell Lymphoma (PMBCL) and other solid tumors. Retrospective studies evaluating the outcomes of alloHCT after prior exposure to CPIs showed favorable survival outcomes but high rates of graft-versus-host disease (GVHD); the risk appears to be lower when using post-transplant cyclophosphamide as GVHD prophylaxis. CPIs have increasingly been used to prevent or treat post-alloHCT relapse. Available data, albeit limited, supports the clinical activity of CPIs in post-alloHCT relapse; however, serious and even fatal cases of GVHD have been reported. The optimal timing, schedule, dosing, and patients likely to benefit from this strategy are yet to be identified. In this review, we highlight the immune system’s role in cancer surveillance and relapse prevention and discuss the current clinical evidence of CPIs use in post-alloHCT relapse.
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