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Resuming Immune Checkpoint Inhibitor Therapy After Immune-Mediated Diarrhea and Colitis

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Key Points

  • Immune-mediated diarrhea and colitis recurred in 34% of patients resuming immune checkpoint inhibitor therapy.
  • Immune-mediated diarrhea and colitis recurrence was more common among patients resuming immune checkpoint inhibitor therapy with anti–CTLA-4 treatment.

In a retrospective multicenter study reported in the Journal of Clinical Oncology, Abu-Sbeih et al found that approximately one-third of patients resuming immune checkpoint inhibitor therapy after improvement in immune-mediated diarrhea and colitis experienced a recurrence of the adverse effect.

The study included 167 patients resuming immune checkpoint inhibitor therapy after improvement in immune-mediated diarrhea and colitis (out of 550 with immune-mediated diarrhea and colitis) between January 2010 and November 2018. Of these, 32 resumed an anti–cytotoxic T-cell lymphocyte-4 (CTLA-4) agent and 135 resumed an anti–programmed cell death protein 1 or ligand 1 (PD-1/PD-L1) agent. The most common cancers in the cohort were melanoma (54%), non–small cell lung cancer (16%), and genitourinary cancer (10%).

Immune-Mediated Diarrhea and Colitis Recurrence

The median duration from immune-mediated diarrhea and colitis to resumption of immune checkpoint inhibitor treatment was 49 days (interquartile range [IQR] = 23–136 days). Among the 167 patients resuming immune checkpoint inhibitor treatment, immune-mediated diarrhea and colitis recurred in 57 patients overall (34%), including 44% of those receiving an anti–CTLA-4 agent and 32% of those receiving an anti–PD-1/PD-L1 agent. In total, 47 of these patients (82%) required immunosuppressive therapy for recurrent immune-mediated diarrhea and colitis, and all had permanent discontinuation of immune checkpoint inhibitor therapy.

The median duration from immune checkpoint inhibitor resumption to immune-mediated diarrhea and colitis recurrence was 53 days (IQR = 22–138 days). On multivariate analysis, patients receiving anti–PD-1/PD-L1 therapy during initial immune-mediated diarrhea and colitis had a higher risk of immune-mediated diarrhea and colitis recurrence vs those receiving anti–CTLA-4 therapy (odds ratio [OR] = 3.45, P = .002).

Those who resumed immune checkpoint inhibitor treatment with anti–PD-1/PD-L1 therapy had a lower risk of recurrence (OR = 0.30, P = .019). Risk of immune-mediated diarrhea and colitis recurrence was higher among patients who required immunosuppression for initial immune-mediated diarrhea and colitis (OR = 3.22, P = .019) or had longer duration of immune-mediated diarrhea and colitis symptoms in the initial episode (OR = 1.01, P = .031).

The investigators concluded, “One-third of patients who resumed immune checkpoint inhibitor treatment after immune-mediated diarrhea and colitis experienced recurrent immune-mediated diarrhea and colitis. Recurrence of immune-mediated diarrhea and colitis was less frequent after resumption of [anti–PD-1/PD-L1 therapy] than after resumption of anti–CTLA-4 [therapy].”

Yinghong Wang, MD, PhD, of the Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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