Anti-PD-1 therapy-induced aGvHD is associated with abnormal IL-1β and NKG2A level in AML patients with relapse post-UCBT

Abstract Relapse is a major cause of death after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). Treatment options for patients who relapse are very limited. Programmed death (PD)-1 blockade has shown therapeutic activity in selected hematologic malignancies, but would trigger severe graft-versus-host disease (GvHD), which is a major obstacle to its success. Herein, we reported the results of sequential PD-1 blockade therapy in patients with relapsed AML after umbilical cord blood transplantation (UCBT). We undertook positron emission tomography–computed tomography to assess the efficacy of sequential PD-1 blockade in patients with AML who relapsed after UCBT. Adequate biopsy analyses revealed an increased number of pro-inflammatory macrophages and increased interleukin-1β (IL-1β) expression in the colon and skin of a patient with severe acute (a)GvHD post-anti-PD-1 therapy. Importantly, we demonstrated low expression of NKG2A in the skin and blood of a patient with aGvHD after anti-PD-1 therapy. Our findings imply that dynamic detection of NKG2A expression in blood or IL-1β expression in tissue could indicate GvHD, and contribute to guiding treatment decisions for sequential PD-1 blockade therapy.