Multiple immune related adverse events among patients with melanoma: Patterns and risk factors.

Abstract

e14651 Background: CheckMate-067 recently trial demonstrated the significant long-term survival benefit of combining ipilimumab and nivolumab versus single-agent immune checkpoint inhibitors (ICIs) in advanced-stage melanoma. While this approach has improved outcomes, melanoma treatment is associated with a high incidence of immune-related adverse events (irAEs), which may be further amplified with dual ICI therapy. Despite this, the development and patterns of multiple irAEs remain poorly understood. This study aimed to elucidate the characteristics and progression of irAEs, with a particular focus on the occurrence of multiple events. Methods: We created an IRB-approved retrospective registry of all melanoma patients who received at least one dose of an ICI between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and outreach clinics. Treatment-emergent adverse events documented in the electronic medical record were reviewed, with attribution and severity estimated using the Common Terminology Criteria for Adverse Events. Case report forms were stored in REDCap and validated with data quality rules. Categorical variables were compared using Chi-squared or Fisher’s exact tests as appropriate, with significance defined as p < 0.05. Results: The cohort comprised 443 patients with a mean age of 63.1 years (SD 13.4). The majority were white (95.9%) and male (67.5%). Most common ICI used were single-agent nivolumab (n = 176, 39.7%), pembrolizumab (n = 110, 24.8%), and ipilimumab (n = 60, 13.5%) while 45 (10%) received nivolumab with ipilimumab. Remaining patients received other combinations. In total, 233 (59.6%) experienced at least irAE. Ipilimumab had the lowest irAE incidence (46.7%) while ipilimumab + nivolumab the highest (80%). Common irAE included dermatitis (n = 75, 16.9%), colitis (n = 61, 13.8%), and thyroid dysfunction (n = 38, 8.6%). Ipilimumab + pembrolizumab showed the highest incidence of dermatitis (n = 7, 31.8%; p = 0.06), while ipilimumab + nivolumab the highest rate of colitis (n = 16, 35.6%; p < 0.01) and thyroid dysfunction (n = 7, 15.6%; p = 0.08). Overall, 141 patients (36.1%) experienced one irAE, 66 (16.88%) had two, 16 (4.09%) experienced three, and 10 (2.56%) were affected by four or more. Incidence of multiple irAE was significantly heterogenous among ICI agents with nivolumab + ipilimumab having highest rates for 1, 2, and > = 4 (16 (35.6%, 16 (35.6%); overall p < 0.01. Conclusions: ICI treatment for melanoma is associated with a heterogeneous risk profile for both individual and multiple irAE. Among the agents studied, the combination of ipilimumab and nivolumab exhibited the highest incidence of irAE affecting different organ systems, as well as the highest rate of multiple irAE. These findings align with the previously demonstrated survival benefits among patients with irAE, reinforcing the potential relationship between irAEs and treatment efficacy. Future translational study into underlying mechanism, especially in the distinct multiple irAE population may be warranted.