Survival outcomes of patients with stage III melanoma treated with adjuvant immunotherapy, with a focus on immune-related adverse events leading to delays in treatment.

Abstract

e21570 Background: Immunotherapy (IO), particularly immune checkpoint inhibitors (ICIs), has demonstrated promising results when used as adjuvant therapy in stage III melanoma, despite the prevalence of immune-related adverse events (irAEs). Although the occurrence of an irAE has been associated with improved survival, irAEs can force delays in therapy that may impact survival outcomes. We present the impact of irAEs on survival in stage III melanoma at a NCI comprehensive cancer center, while focusing on the implications of delaying therapy due to irAEs. Methods: Chart review identified 178 patients with stage III melanoma that were treated with adjuvant IO. Overall survival (OS) was measured from the onset of IO to death and was censored at last follow-up for survivors. Progression-free survival (PFS) was measured from the onset of IO to relapse or death and was censored at last follow-up for those alive without disease progression. The effect of irAE on OS and PFS was evaluated using the multivariable Cox model, adjusting for the effect of demographic and clinical factors. All tests are two-sided and p-values < 0.05 were considered statistically significant. Results: Most patients (56.2%) were male, with a median age of 61 years (range (R): 24 – 94 years, interquartile range (IQR): 21 years) at time of diagnosis and had the following staging breakdown: 15.7% IIIA, 29.8% IIIB, 46.6% IIIC, and 6.7% IIID. 41.0% of patients experienced an irAE, with dermatitis, hypothyroidism, and colitis the most common types of irAE (Table 1). There was no significant difference in OS or PFS in those who experienced an irAE versus those who did not experience an irAE after controlling for stage, age, gender, and BMI. 65.8% of patients who experienced an irAE paused treatment due to the irAE, with a median delay of 56 days (R: 3 – 140 days, IQR: 27 days). 64% of patients did not resume first-line therapy. 77.8% of irAEs were low grade (I-II), and 100% of patients who experienced high grade (III-IV) irAE paused therapy. IrAE grade had a significant impact on OS, with 91% OS for those without irAE, 96% OS for those with low grade and 81% OS for those with high grade irAE after 1 year (p = 0.0173). Pausing treatment on its own did not have a significant impact on PFS or OS. Conclusions: The presence of an irAE did not impact OS or PFS in this subset of patients with stage III melanoma, contrary to prior studies. High grade irAEs led patients to pause therapy and have worse OS, although pausing treatment by itself did not impact survival. Further analysis is warranted to examine if duration of paused therapy or prompt resumption of IO after an irAE affects survival. Distribution of irAEs. Type of irAE Frequency (%) Dermatitis 16 (21.9) Hypothyroidism 13 (17.8) Colitis 11 (15.1) Hepatitis 6 (8.2) Adrenal Insufficiency 3 (4.1) Myocarditis 3 (4.1) Thyroiditis 3 (4.1) Pneumonitis 2 (2.7) Other 16 (21.9)