Unchecked immunity: a unique case of sequential immune-related adverse events with Pembrolizumab

Abstract

Background: Immune checkpoint inhibition has dramatically transformed the treatment of malignant melanoma. With increasing use, their unique spectrum of immune-mediated toxicity has become apparent.

Case presentation: We describe a case of sequential immune-related adverse events (irAEs) in a patient with metastatic melanoma treated with single-agent anti-programmed cell death-1 (PD-1) therapy, pembrolizumab. Although numerous cases of irAEs have been reported, sequential multi-organ involvement, including progressive atopic dermatitis, vitiligo, autoimmune nephritis, autoimmune hepatitis, and autoimmune encephalitis after cessation of therapy, has not been previously documented.

Conclusions: Immunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation.

Keywords: Checkpoint inhibitors; Immune-related adverse events; Malignant melanoma.

Fig. 1

( a ) Timeline of diagnosis, treatment and immune-related adverse events ( b ) Post-treatment PET scan from April 2017: Initial L inguinal mass, as well as cerebral metastasis have resolved. Unrelated persistent bilateral parotid FDG-avidity which remained stable over serial PET scans ( c ) Replacement of the lymph node tissue by diffuse infiltrate of large malignant cells with occasional intranuclear inclusions (black arrows) [400x]. ( d ) Metastatic melanoma diagnosis confirmed by strong nuclear positivity for SoX-10 on immunohistochemical staining [200x] and ( e ) diffuse S-100 positivity [200x]. Immunostaining of tumour infiltrating lymphocytes showing positivity for T-cell markers ( g ) CD4 [200x], and ( h ) CD8 [200x]

Fig. 2

Kidney biopsy showing active tubulointerstitial nephritis ( a ) Interstitial inflammation with moderate numbers of eosinophils, small lymphocytes, and neutrophils [200x]. ( b ) Immunostaining of interstitial lymphocytes showing positivity for T-Cell markers CD4 [200x], and (c) CD8 [200x]. The liver biopsy showing features of autoimmune hepatitis process [200x] ( d ) Portal tract fibrosis with moderate inflammation, periportal hepatocyte ballooning, and focal necrosis. ( e ) Lobular activity with areas of necrosis and inflammation around central vein (black arrows) [200x] ( f ) Confluent necrosis highlighted by PAS stain [100X]. ( g ) Immunostaining of portal and periportal lymphocytes showing positivity for T-Cell markers CD4 [200x], and (H) CD8 [200x]