Abstract 872P
Background
There is a paucity of population-based data regarding ipilimumab-induced gastrointestinal and hepatic immune-related adverse events (irAE) during cutaneous melanoma treatment. We examined the risk and predictors of gastrointestinal and hepatic irAE in a national cohort of patients diagnosed with cutaneous melanoma.
Methods
This retrospective study used Surveillance, Epidemiology and End Results - Medicare linked data of patients diagnosed with cutaneous melanoma between the years 2010 and 2015 treated with ipilimumab or other therapies. We excluded patients with preexisting gastrointestinal and hepatic conditions. Our endpoint was time to gastrointestinal and hepatic irAE after treatment. We used multivariable competing-risk analysis adjusted for death of any cause within one year of treatment as a competing event to estimate the risk of gastrointestinal and hepatic irAE. Then, we used a stepwise competing-risk model to assess the predictors of having at least one gastrointestinal and hepatic irAE among patients treated with ipilimumab. The covariates included were patient demographics, disease stage, prevalent autoimmune disease, history of hypertension, anticoagulant use, end-stage renal disease, steroid use, and Charlson Comorbidity Index.
Results
Overall, 620 out of 31,234 (2%) patients were treated with ipilimumab. Incidence rates of gastrointestinal and hepatic irAE among patients who received ipilimumab and controls were 32.3 and 4.0 per 1,000 person-years, respectively. Receiving ipilimumab was associated with an increased risk of gastrointestinal and hepatic irAE compared to controls (HR: 10.18, 95% CI: 8.11-12.78, p<.001). Other predictors of gastrointestinal and hepatic irAE are found in the table. Table: 872P
Significant predictors of gastrointestinal and hepatic immune-related adverse events
| Entire Cohort (n=31,234) | Ipilimumab Cohort (n=620) | |||||
| Covariant | Hazard Ratio † | 95 % Confidence Interval | p-value | Hazard Ratio ‡ | 95 % Confidence Interval | p-value |
| Ipilimumab | 10.18 | 8.11 – 12.78 | <.001 | NA | NA | NA |
| Year of Diagnosis | 0.88 | 0.84 – 0.91 | <.001 | - | - | - |
| Gender | 1.20 | 1.04 – 1.38 | =.011 | - | - | - |
| Charlson Comorbidity Index | 1.48 | 1.09 – 2.01 | =.011 | - | - | - |
| Autoimmune Disease | 1.53 | 1.25 – 1.88 | <.001 | 0.26 | 0.09 – 0.83 | =.023 |
| Hypertension | 1.53 | 1.28 – 1.83 | <.001 | - | - | - |
| Anticoagulant | 1.34 | 1.11 – 1.60 | =.002 | - | - | - |
- Not significant at 0.05 threshold † Competing risk model (Fine & Gray method) ‡ Stepwise competing risk model.
Conclusions
Patients treated with ipilimumab had higher risk of gastrointestinal and hepatic irAE than controls.Among patients who received ipilimumab, history of autoimmune disease was associated with lower risk of irAE.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Brigham And Women's Hospital.
Funding
Has not received any funding.
Disclosure
J. McNabb-Baltar: Financial Interests, Personal, Advisory Board: Nestle Health. M. Sun: Financial Interests, Personal and Institutional, Research Grant: Department of Defense , National Institute of Health , Bristol Myers Squibb , Fonds de recherche du Québec en Santé . A. Cole: Financial Interests, Personal and Institutional, Funding: American Cancer Society, Pfizer Global Medical Grants. Q. Trinh: Financial Interests, Personal, Other: Astellas, Bayer , Janssen ; Financial Interests, Personal and Institutional, Funding: American Cancer Society, Defense Health Agency, Pfizer Global Medical Grants. All other authors have declared no conflicts of interest.