A review of single agent and combination immunotherapy-induced colitis from a tertiary referral centre in Australia

Abstract

Background: Autoimmune colitis secondary to ipilimumab is well described. Newer immunotherapy agents such as PD1/PD-L1 inhibitors are now used as single agents or in combination with ipilimumab. The clinical course of colitis due to PD1 inhibitors and combination immunotherapies has yet to be clearly outlined. We report a retrospective case series of patients with immunotherapy-induced autoimmune colitis from a tertiary referral centre in Australia. Method(s): All patients at Westmead Hospital with autoimmune colitis from 2011 were identified from the melanoma database, clinical trials databases and medical records coding. Three cohorts were formed according to treatment with single agent ipilimu-mab, single agent PD1/PDL1 inhibitor or combination of both. Result(s): From 2011, 18 cases of immunotherapy-induced colitis were identified (12 male, 6 female). 14 patients were treated for melanoma, two for renal cell carcinoma and two for non-small cell lung cancer. 6 patients were on combination immunother-apy, 6 on ipilimumab alone, and 6 on PD1/PDL1 inhibitor alone. The combination group had more episodes of grade 3 colitis (5), versus 2 in each single agent group, and five hospital admissions compared to 3 in the PD1 cohort and 2 in the ipilimumab cohort. PD1-colitis had a slower onset of symptoms from the start of treatment, with a median of 14.8 weeks, comparedto6 weeks for ipilimumab alone and8 weeks for combination therapies. Only one patient in the PD1-colitis group had a raised WCC on presentation, with a median WCC of 6.4 and median CRP of 5.1, versus 9.4 and 47.5 for the ipilimumab cohort and 11.25 and 35 for the combination cohort. There was no statistically significant difference in severity and distribution of colitis on endoscopy. Three patients in the combination group required infliximab versus two in the PD1-colitis group and one in the ipilimumab group. The median time to resolution of symptoms was 34 days in the combination group, 60 days in the ipilimumab group and 65 days in the PD1 group. Five patients had a relapse during steroid wean. Three patients in the ipilimumab cohort and one patient in the combination group were re-challenged with a PD1 inhibitor without recurrence of colitis. Disease control rate was 58%. Those with progressive disease had a median survival of 11 months. Conclusion(s): Combination immunotherapy resulted in more severe colitis, requiring more hospital admissions and infliximab therapy. PD1-inhibitors caused an indolent subacute phenotype. Relapse during steroid wean was common, highlighting the need for a slow and cautious steroid dose reduction. Patients with ipilimumab-colitis were safely re-challenged with PD1 inhibitors.