Delayed Autoimmune Toxicity Occurring Several Months After Cessation of Anti-PD-1 Therapy

Abstract

Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved. This study describes for the first time a case of delayed autoimmunity occurring 8 months after discontinuing treatment with the anti-PD-1 antibody nivolumab in a patient with metastatic melanoma. The case highlights the need for ongoing surveillance of patients treated with immune checkpoint inhibitors even after cessation of therapy, especially as patients increasingly stop treatment after achieving durable responses.

Figure 1.

Positron emission tomography‐computed tomography images. (A): Sites of metastatic disease prior to commencing nivolumab. (B): Four months after commencement of nivolumab, a complete response was seen in all sites of disease apart from a solitary progression of a left adrenal gland metastasis. (C): The patient maintained a complete response after completion of radiotherapy to the left adrenal gland.

Figure 2.

Time course of liver function tests. Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ‐glutamyltransferase.