Abstract 3732
Background
Colitis is one of the major immune-related adverse events (irAEs) to immunotherapy that leads to significant morbidity and discontinuation of treatment. Despite being a frequent irAE, clinical presentation, endoscopic and pathological features, and management of colitis in patients (pts) treated with combination IPI+PD1 and PD1 monotherapy are not well- defined.
Methods
Pts with locally advanced or metastatic melanoma who received combination IPI+PD1 or PD1 monotherapy and developed clinically significant colitis (requiring systemic corticosteroids) were identified retrospectively from 2 academic centers. Clinical data were collected on all pts; endoscopic and histopathologic data were examined on a subset.
Results
112 patients were identified who developed significant colitis between May 2013 and October 2018; 73 treated with IPI+PD1 and 33 treated with PD1 monotherapy. Six pts were excluded from the analysis that received ipilimumab alone (3 pts) or received treatment (3 pts) on clinical trials (blinded). Endoscopic and histopathologic data were available on 63 pts. Combination therapy induced colitis was earlier onset (8.8 weeks vs 44.6 weeks, p < 0.0001) and more severe (Grade 3/4; 66% vs 31%, p = 0.0014) than with monotherapy. Infliximab and immunosuppressive agents beyond corticosteroids were required in most pts with combination therapy (54% vs 30% with monotherapy, p = 0.02). Five pts (3 combination, 2 monotherapy) underwent colectomy due to complicated steroid refractory disease (3/5 were infliximab refractory). There were no colitis related deaths. The presence of moderate to severe, diffuse inflammation was more common on combination therapy than monotherapy (51% vs 33%, p = 0.36). A chronic inflammatory infiltrate was more common on histopathology with combination colitis compared to monotherapy (46% vs 20%, p = 0.12).
Conclusions
Clinically significant colitis due to immunotherapy varies in presentation, response to immunosuppression and endoscopic/histologic features. IPI+PD1 colitis has an earlier onset, is more severe yet resistant to corticosteroids than PD1 induced colitis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.S. Carlino: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. R.A. Scolyer: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: Myriad; Advisory / Consultancy: NeraCare. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: BMS; Advisory / Consultancy: MERCK MSD; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.
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