Fatal Immune Response Associated with Anti-PD1: Pathological Insight

Case Report

Ann Hematol Oncol. 2021; 8(6): 1349.

Fatal Immune Response Associated with Anti-PD1: Pathological Insight

Supari D¹*, Meyer J², Heindl U², Karthaus M³, Pohlmann H³, Hann von Weyhern C¹ and Kremer M¹

1Institute of Pathology, Klinikum Neuperlach, Munich, Germany

2Department of Pulmonology, Gastroenterology und Emergency Medicine, Klinikum Harlaching, Munich, Germany

3Department of Hematology, Oncology und Palliative Medicine, Klinikum Neuperlach, Munich, Germany

*Corresponding author: Divya Supari, Municipal Hospital of Munich, Klinikum Neuperlach, Oskar-Maria- Graf-Ring 52, 81737 Munich, Germany

Received: April 07, 2021; Accepted: May 13, 2021; Published: May 20, 2021


The recent introduction of immune checkpoint inhibitor therapy with anti- PD-1 agents has shown encouraging responses in gastrointestinal oncology. However, it is also known to possibly result in uncontrolled T cell autoreactivity, leading to a broad range of immune related adverse events.

We present a patient who developed sequential immune-related hematologic and hepatic complications following pembrolizumab therapy for metastatic colon cancer. In particular, we describe in detail the histopathologic and immunohistochemical findings in the liver and bone marrow, adding to the spectrum of morphological changes which may be observed in association with PD-1 inhibitor therapy.

The report also highlights the occurrence of these adverse reactions even after discontinuation of immunotherapy, eventually resulting in the death of the patient.

Keywords: Colon cancer; Immune checkpoint inhibitor therapy; Anti-PD-1; Neutropenia; Hepatitis; Thrombocytopenia; Immune-related adverse events

Case Presentation

An 85-year-old man was diagnosed in October 2017 with adenocarcinoma of the colon ascendens. He underwent right side hemicolectomy. Pathological examination of the specimen revealed a colon adenocarcinoma NOS with UICC stage IIIA (pT3, pN1a (1/19), pM0, L1, V0), MSI-H. Fourteen months later, in December 2018, surveillance computed tomography (CT) findings showed multiple enlarged retroperitoneal and para-aortic lymph nodes. Subsequently performed lymph node biopsies confirmed metastatic infiltration of colon adenocarcinoma. The patient was subsequently treated with nine cycles of pembrolizumab (200mg every three 3 weeks) from December 2018 to June 2019.

Two weeks after completion of the ninth cycle of pembrolizumab, the patient was hospitalized due to severe febrile neutropenia with an absolute neutrophil count (ANC) of 0/μl. The serological markers for hepatitis A, B, C, HSV and CMV were tested negative. Blood and urine cultures performed were negative. Bone Marrow (BM) aspiration and trephine biopsy findings are described in detail below. Pembrolizumab was discontinued. The patient was subsequently treated with meropenem (1g daily), Granulocyte Colony-Stimulating Factor (G-CSF) (34 million IU per day) and high-dose oral prednisone (100mg daily). After 4 weeks he had recovery of his neutrophil count with ANC of 2500/μL. Other blood counts were within the normal limits.

In early August the patient was diagnosed with invasive pulmonary aspergillosis based on serum Aspergillus galactomannan antigen by enzyme immunoassay (index 1.10) combined with bilateral pulmonary infiltrate on CT images. Intravenous voriconazole followed by oral therapy was initiated. Prior to voriconazole therapy the liver transaminases were mildly elevated with an aspartate aminotransferase (AST) level of 36U/L (normal range: <35U/L) and an alanine aminotransferase (ALT) level of 117U/L normal range: <45U/L). After 10 days of treatment with voriconazole, the transaminases peaked and then gradually decreased with dose reduction of voriconazole (Figure 1). Seven weeks later voriconazole was terminated as his symptoms improved and his CT chest showed a marked resolution of pre-existing aspergillosis associated lesions.