Concurrent immune checkpoint inhibition and selective immunosuppressive therapy in patients with immune-related enterocolitis

Yousef R. Badran, Fangwen Zou, Sienna M. Durbin, Barbara E. Dutra, Hamzah Abu-Sbeih, Anusha S. Thomas, Mehmet Altan, John A. Thompson, Wei Qiao, Donna E. Leet, Po Ying Lai, Nora K. Horick, Michael A. Postow, David M. Faleck, Yinghong Wang, Michael Dougan

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-related enterocolitis (irEC). We examined the effect of resumption of ICIs with or without concurrent selective immunosuppressive therapy (SIT) on rates of symptom recurrence and survival outcomes. Methods: This retrospective, multicenter study examined patients who were treated with ICI and developed irEC requiring SIT (infliximab or vedolizumab) for initial symptom control or to facilitate steroid tapering between May 2015 and June 2020. After symptom resolution, patients were restarted either on ICI alone or on concurrent ICI and SIT at the discretion of the treating physicians. The associations between irEC recurrence and treatment group were assessed via univariate analyses and multivariate logistic regression. Cox proportional hazards model was used for survival analysis. Results: Of the 138 included patients who required SIT for initial irEC symptom control, 61 (44.2%) patients resumed ICI without concurrent SIT (control group) and 77 (55.8%) patients resumed ICI therapy with concurrent SIT: 33 with infliximab and 44 with vedolizumab. After symptom resolution, patients in the control group were more commonly restarted on a different ICI regimen (65.6%) compared with those receiving SIT (31.2%) (p<0.001). The total number of ICI doses administered after irEC resolution and ICI resumption was similar in both groups (four to five doses). Recurrence of severe colitis or diarrhea after ICI resumption was seen in 34.4% of controls compared with 20.8% of patients receiving concurrent SIT. Concurrent SIT was associated with reduced risk of severe irEC recurrence after ICI resumption in a multivariate logistic regression model (OR 0.34; 95% CI 0.13 to 0.92; p=0.034). There was no difference in survival outcomes between patients in the control group and patients concurrently treated with SIT. Conclusion: After resolution of irEC symptoms, reinitiation of ICI with concurrent SIT is safe, reduces severe irEC recurrence, and has no negative impact on survival outcomes.

Original languageEnglish
Article numbere007195
JournalJournal for ImmunoTherapy of Cancer
Volume11
Issue number6
DOIs
StatePublished - 22 Jun 2023
Externally publishedYes

Keywords

  • Autoimmunity
  • Immune Checkpoint Inhibitors
  • Immunotherapy
  • Inflammation

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