Association of Multisystem Immune-Related Adverse Events and Survival in Patients with NSCLC

Anti-programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) are a vital part of the therapeutic setting for non-small cell lung cancer (NSCLC). On the other hand, scientists noted that immune-related adverse events (irAE’s) may cause morbidity and mortality in patients. Large case series studies in NSCLC and other tumors have identified that irAE development is associated with improved survival outcomes. The prevalence, clinical patterns, and survival implications for patients who develop irAEs involving multiple organ systems (multi-system irAEs) are unknown, although the range of individual irAEs has been widely reported. This multicenter cohort study characterizes the spectrum of multisystem irAEs, their association with survival, and risk factors for the development of multisystem irAE in patients with NSCLC treated with ICIs. It was reported that NSCLC patients treated with anti-PD (L)-1 ICI were identified in 5 academic centers in the study. The study included patients 18 years of age or older with pathologically confirmed stage III/IV NSCLC who received 1 dose or more of anti-PD(L)-1 monotherapy or anti-PD(L)-1 based combinations. This retrospective cohort study was reported to include 623 patients with stage III/IV NSCLC, treated with anti–PD-(L)1 ICIs alone or in combination with another anticancer agent between January 2007 and January 2019. Patient irAEs were identified by the treating oncologist based on evidence of pathological irAE, multidisciplinary judgment involving 2 or more oncologists, or clinical improvement with irAE-based therapy, respectively.

Multi-system irAE patterns

Researchers stated that multi-system irAEs are described as irAEs involving more than one organ system. They were characterized by combinations of individual irAEs or organ systems involved, separated by ICI-monotherapy or combinations. Median progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method while differences in PFS and OS between irAE groups were assessed by multivariable models. The risk for multisystem irAE was estimated as odds ratios by multivariable logistic regression. The 623 patients included in the study were mostly men and white. The researchers reported that the median (range) age was 66, and that 148 patients developed a single irAE, whereas 58 developed multisystem irAEs. The most common multisystem irAE patterns in patients receiving anti-PD-(L)1 monotherapy during the study were pneumonitis thyroiditis, hepatitis thyroiditis, dermatitis pneumonitis and dermatitis thyroiditis. The researchers expressed that favorable Eastern Cooperative Oncology Group (ECOG) performance status (PS) and longer ICI duration were independent risk factors for development of multisystem irAEs. The study’s findings revealed that patients with 1 irAE and multisystem irAEs demonstrated incrementally improved OS and PFS vs patients with no irAEs, in multivariable models adjusting for ICI duration. The researchers stated that this study identified multisystem irAE patterns in patients with NSCLC treated with ICIs, but also demonstrated an association between multiple system irAEs and survival.