Association of CT-assessed sarcopenia and the development of immune-related adverse events and overall survival: a multistate survival analysis

Background: Immune checkpoint inhibitors (ICIs) have improved survival in non-small cell lung cancer (NSCLC), yet identifying who benefits from treatment remains difficult. Low skeletal muscle mass (SMM) is associated with poor cancer outcomes. We aim to examine the relationship between computed tomography (CT)-assessed sarcopenia and patient trajectories [death, immune-related adverse events (irAEs) and death after irAEs] following ICI initiation. Methods: We conducted a retrospective cohort study of NSCLC patients treated with ICIs at the University Medical Center Groningen [2015-2021] with baseline low-dose computed tomography (LDCT) scans. Sarcopenia was defined using sex-specific SMM thresholds. Multi-state time-to-event models estimated transition probabilities between ICI initiation and three outcomes: direct mortality (without irAEs), development of irAEs, and mortality after irAEs. Models were adjusted for age, sex, performance status, cancer stage, treatment line, body mass index (BMI), and combination therapy. Separate models were built for severe and any-grade irAEs. Results: Among 363 patients (96-month follow-up), 301 (82.9%) died and 166 (45.7%) developed irAEs, including 76 (20.9%) with severe irAEs. In the severe irAE model, sarcopenia was not associated with developing severe irAEs [hazard ratio (HR) =0.81, 95% confidence interval (CI): 0.42-1.58] or with mortality without severe irAEs (HR =1.19, 95% CI: 0.82-1.74). However, sarcopenia was associated with reduced mortality after severe irAEs (HR =0.39, 95% CI: 0.23-0.65). In the any-grade irAEs model, sarcopenic patients were less likely to develop irAEs (HR =0.63, 95% CI: 0.42-0.93). Sarcopenia was not linked to mortality without irAEs (HR =1.08, 95% CI: 0.70-1.67) or after any-grade irAEs (HR =0.81, 95% CI: 0.52-1.26). Conclusions: In this NSCLC cohort, CT-assessed sarcopenia was not associated with direct mortality without irAEs but was linked to a lower likelihood of developing irAEs and reduced mortality after severe irAEs. These findings suggest that body composition may have prognostic value and influence responses to immunotherapy.