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.
Resources from the same session
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract
5056 - Phase 2 study of 2 dosing regimens of cemiplimab, a human monoclonal anti–PD-1, in metastatic cutaneous squamous cell carcinoma (mCSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
5710 - Avelumab for advanced Merkel cell carcinoma in the Netherlands; a nationwide survey
Presenter: Sonja Levy
Session: Poster Display session 3
Resources:
Abstract
3152 - Health-related quality of life in patients with metastatic Merkel cell carcinoma receiving second-line or later avelumab treatment: 36-month follow-up data
Presenter: Sandra D'Angelo
Session: Poster Display session 3
Resources:
Abstract
5715 - A Phase 2, Randomized Study of Nivolumab (NIVO) and Ipilimumab (IPI) versus NIVO, IPI and Stereotactic Body Radiation Therapy (SBRT) for Metastatic Merkel Cell Carcinoma (MCC, NCT03071406) – a preliminary report.
Presenter: Sungjune Kim
Session: Poster Display session 3
Resources:
Abstract
2854 - Real-world impact of immune checkpoint inhibitors in metastatic uveal melanoma
Presenter: Kalijn Bol
Session: Poster Display session 3
Resources:
Abstract
2928 - Immune checkpoint inhibitors in a cohort of 206 metastatic uveal melanomas patients
Presenter: Mathilde Saint-Ghislain
Session: Poster Display session 3
Resources:
Abstract
1235 - Incidence and survival of Uveal Melanoma occurring as single cancer versus its occurrence as a first or second primary neoplasm
Presenter: Ahmad Alfaar
Session: Poster Display session 3
Resources:
Abstract
3615 - Validation of a Clinicopathological and Gene Expression Profile (CP-GEP) Model for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
Presenter: Evalyn Mulder
Session: Poster Display session 3
Resources:
Abstract
1793 - External validation of the 8th Edition Melanoma Staging System of the American Joint Committee on Cancer (AJCC) using the Surveillance, Epidemiology and End Results (SEER) Program
Presenter: Angelina Tjokrowidjaja
Session: Poster Display session 3
Resources:
Abstract