Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors

Shaleen Vasavada; Kavea Panneerselvam; Rajan Amin; Krishnavathana Varatharajalu; Pablo C Okhuysen; Isabella C Glitza Oliva; Jianbo Wang; Petros Grivas; Anusha S Thomas; Yinghong Wang

doi:10.20524/aog.2022.0722

Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors

Ann Gastroenterol. 2022 Jul-Aug;35(4):393-399. doi: 10.20524/aog.2022.0722. Epub 2022 Jun 2.

Affiliations

¹ Department of Internal Medicine, Baylor College of Medicine, Houston, Texas (Shaleen Vasavada, Kavea Panneerselvam).
² Department of Internal Medicine, The University of Texas Health Science Center, Houston, Texas (Rajan Amin).
³ Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas (Krishnavathana Varatharajalu, Anusha S. Thomas, Yinghong Wang).
⁴ Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas (Pablo C. Okhuysen).
⁵ Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Isabella C. Glitza Oliva).
⁶ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Jianbo Wang).
⁷ Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, Washington (Petros Grivas), USA.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but are associated with immune-mediated diarrhea and colitis (IMDC). Clostridioides difficile infection (CDI) can cause infectious diarrhea with overlapping symptoms. Thus, we sought to elucidate the characteristics of CDI in patients treated with ICI, in the context of IMDC.

Methods: We conducted a retrospective, single-center study of adult cancer patients (N=421) with ICI exposure from 2015-2020 and a positive stool nucleic acid amplification test and/or enzyme immunoassay for CDI. Baseline characteristics, treatments, and outcomes were compared between patients with and without concurrent IMDC.

Results: Forty-one eligible patients were included, 27 with concurrent IMDC and 14 without. Twenty-seven patients were taking programmed death-1 or its ligand inhibitors and 14 were taking cytotoxic T-lymphocyte-associated antigen 4 inhibitors. Patients with concurrent CDI and IMDC had a longer symptom duration (20 vs. 5 days, P=0.003) and a higher rate of grade 3-4 diarrhea (41% vs. 7%, P=0.033). Among patients with concurrent IMDC, preceding antibiotics (P=0.050) and proton pump inhibitors (PPI) (P=0.038) were used more frequently among individuals who developed CDI after immunosuppressant exposure. Thirty-eight patients received antibiotics for CDI, while 5 required fecal microbiota transplantation for concurrent CDI & IMDC.

Conclusions: CDI is common in ICI-treated cancer patients, especially those with IMDC requiring immunosuppressants. Antibiotics did not alter the need for immunosuppressants in those with concurrent IMDC. Use of PPI and antibiotics while receiving immunosuppressants for IMDC was associated with a greater risk of CDI. Further large-scale studies are warranted to clarify the role of CDI, antibiotics and immunosuppression treatment in IMDC patients.

Keywords: Clostridioidesdifficile infection; Immune checkpoint inhibitors; immune-mediated diarrhea and colitis.