Toxicity associated with PD-1 blockade after allogeneic haematopoietic cell transplantation

Abstract

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) such as programmed death ligand-1 (PD-L1) blockers offers pronounced clinical benefit with durable responses and a manageable safety profile. Patients with a high risk of immune-related adverse events are generally excluded from clinical trials testing ICI therapy. Thus, only a little information on the safety and clinical outcome of patients treated with an ICI after allogeneic haematopoietic cell transplantation (HCT) is currently available. Here, we report the characteristics and outcomes of six patients with, respectively, clear cell renal carcinoma, diffuse large cell B-cell lymphoma, Hodgkin lymphoma, a microsatellite instable colorectal cancer and melanoma who were treated with PD-1 blocking antibodies. All patients had previously undergone allogeneic HCT. Severe grade 3–5 immune-related adverse events were observed in three of five patients who received full-dose ICI therapy. One patient received a lower dose of PD-1 blocking antibody. Only one patient had an objective response, whereas all the other patients had progressive disease. The high toxicity of a full- dose anti-PD-1 treatment regimen suggests that other treatment approaches for patients after allogeneic HCT are needed outside of the context of relapsed Hodgkin disease. In cases where ICI therapy is the only treatment option, reduced dosing should be explored.

Keywords

• CTLA-4
• graft-versus-host disease (GvHD)
• immune-related adverse event (irAE)
• Immunotherapy
• PD-1