JAK Inhibitor Upadacitinib Induces Remission in Refractory Immune-Related Colitis Triggered by CTLA-4 and PD-1 Inhibitor Combination Therapy in Malignant Pleural Mesothelioma: A Case Report

Cancer Rep (Hoboken). 2024 Oct;7(10):e70032. doi: 10.1002/cnr2.70032.

Abstract

Background: Immune checkpoint inhibitors have demonstrated efficacy against various cancers; however, there is a rising incidence of immune-related colitis. Some cases of immune-related colitis prove resistant to treatment, even with the administration of glucocorticoids or infliximab, and there is currently no established standard treatment for such cases.

Case: The patient, a 73-year-old male, had undergone combination therapy for malignant pleural mesothelioma for 2 years, utilizing both ipilimumab (a CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor). Unfortunately, the treatment led to side effects, specifically immune-related adverse event (irAE) enterocolitis. Steroid and infliximab treatment failed to improve the patient's condition. Treatment with tacrolimus was attempted, but the patient remained unresponsive. Subsequently, 45 mg of upadacitinib, a Janus kinase (JAK) inhibitor, was administered. Symptoms improved rapidly following upadacitinib administration, and endoscopy also revealed positive results. With the increasing incidence of immune-related colitis, some patients have become resistant to treatment with glucocorticoids and infliximab. In this case, the irAE enterocolitis was improved by upadacitinib administration.

Conclusion: In cases where immune-related colitis proves resistant to treatment with glucocorticoids, infliximab, or tacrolimus, upadacitinib represents a potential option as a JAK inhibitor.

Keywords: CTLA‐4 inhibitor; JAK inhibitor; PD‐1 inhibitor; irAE; upadacitinib.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • CTLA-4 Antigen / antagonists & inhibitors
  • Colitis / chemically induced
  • Colitis / diagnosis
  • Colitis / drug therapy
  • Colitis / immunology
  • Heterocyclic Compounds, 3-Ring* / administration & dosage
  • Heterocyclic Compounds, 3-Ring* / adverse effects
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / adverse effects
  • Ipilimumab* / administration & dosage
  • Ipilimumab* / adverse effects
  • Janus Kinase Inhibitors* / administration & dosage
  • Janus Kinase Inhibitors* / adverse effects
  • Janus Kinase Inhibitors* / therapeutic use
  • Lung Neoplasms / drug therapy
  • Male
  • Mesothelioma, Malignant* / drug therapy
  • Mesothelioma, Malignant* / pathology
  • Nivolumab / administration & dosage
  • Nivolumab / adverse effects
  • Nivolumab / therapeutic use
  • Pleural Neoplasms / drug therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Remission Induction

Substances

  • upadacitinib
  • Janus Kinase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Immune Checkpoint Inhibitors
  • Ipilimumab
  • Nivolumab
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • CTLA4 protein, human