Objective: Immune checkpoint inhibitor (ICI) combination therapy has higher efficacy than ICI monotherapy but is associated with a high grade 3 or 4 immune-related adverse event (irAE) incidence. Since ICI treatment is performed in outpatient settings, irAE monitoring is challenging. We elucidated risk factors for early irAE detection and prevention.

Patients and Methods: We retrospectively investigated factors related to irAE severity and their impact on survival in patients with non-small cell lung cancer (NSCLC) receiving nivolumab plus ipilimumab at our center from January 2020 to December 2022.

Results: Baseline platelet count and platelet-to-lymphocyte ratio (PLR) were higher in the grade 3 or higher group than in the grade 2 or lower group (median, 314 × 103/μL and 288 vs. 227 × 103/μL and 150; p = 0.035 and 0.010, respectively). irAE grade and number of multisystem irAEs were positively correlated; 83% of patients in the grade 3 or higher group had multisystem irAEs. Using a PLR cutoff of 204 (determined using receiver operating characteristic curves), all patients with grade 3 or higher irAEs were in the PLR ≥ 204 group, representing 66.7% of patients. Severe irAE presence was associated with prolonged overall survival (OS) (p = 0.081). Progression-free survival and OS were longer in patients with multisystem irAEs than in those without (p = 0.004 and 0.016, respectively).

Conclusions: Multisystem irAEs are associated with a better prognosis in patients with NSCLC receiving nivolumab plus ipilimumab. Determining platelet count and PLR immediately before this regimen may help predict the occurrence of severe irAEs.