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

Our plain-English summary of 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, by M. Kono, Y. Komeda, H. Kawakami, et al (Cancer Reports, 2024).

The study

• Authors: M. Kono, Y. Komeda, H. Kawakami, S. Hagiwara, G. Tribonias, K. Handa, S. Omoto, M. Takenaka, H. Kashida, N. Tsuji, M. Kudo
• Journal: Cancer Reports
• Published: 2024;7(10):e70032
• Type of article: Case report
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.

In plain English

This case report described one patient, a 73-year-old man diagnosed with malignant pleural mesothelioma in August 2021. He had been treated for 2 years with two immune checkpoint inhibitor drugs, ipilimumab (a CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor). The article does not discuss asbestos exposure. In March 2023 he developed severe watery diarrhea caused by immune-related bowel inflammation (irAE enterocolitis), rated CTCAE grade 3. Steroids (60 mg/day) and infliximab (5 mg/kg) did not improve his condition, and he was transferred to Kindai University Hospital. Biopsies there also showed CMV enteritis and pseudomembranous enteritis, which were treated. Two weeks of tacrolimus did not help. He was then given 45 mg of the JAK inhibitor upadacitinib. Within a few days his bowel movements fell from more than 10 to fewer than 3. The dose was lowered to 15 mg after 8 weeks with no recurrence. Endoscopy confirmed mucosal remission after about 6 months, and the drug was stopped. There was no recurrence over the next 6 months and no progression of the mesothelioma. The authors concluded that upadacitinib is a promising option for such patients and called for prospective trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient)
• Who was studied: One 73-year-old man who presented with bilateral pleural effusions in June 2021, was diagnosed with malignant pleural mesothelioma in August 2021, and was later transferred to Kindai University Hospital (Osaka, Japan)
• Exposure: Two years of combination immune checkpoint inhibitor therapy for malignant pleural mesothelioma: ipilimumab (CTLA-4 inhibitor) plus nivolumab (PD-1 inhibitor). Asbestos exposure is not discussed.
• Main results:
  • In March 2023 the patient developed watery diarrhea more than 10 times a day (irAE enterocolitis), graded CTCAE grade 3
  • Steroids (60 mg/day) and infliximab (5 mg/kg) did not improve the patient's condition
  • Colonic biopsy also showed CMV enteritis and pseudomembranous enteritis
  • Two weeks of tacrolimus produced no response, so 45 mg of upadacitinib was given
  • After upadacitinib, the patient's defecation frequency fell from more than 10 to less than 3 within a few days
  • The upadacitinib dose was reduced to 15 mg after 8 weeks, with no recurrence
  • Endoscopy confirmed mucosal remission after about 6 months, and upadacitinib was discontinued
  • No recurrence in the 6 months after stopping upadacitinib, and no progression of the malignant pleural mesothelioma
• The authors' conclusion: The authors concluded that upadacitinib is a promising treatment option for patients with immune-related adverse events that do not respond to conventional therapies
• Limitations the authors state:
  • The authors stated that prospective trials are needed to evaluate the long-term safety and efficacy of upadacitinib

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: CTLA-4, Pleural Mesothelioma, checkpoint inhibitors, Ipilimumab (Yervoy), Nivolumab (Opdivo), Endoscopy.

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