Incidence and Immunopathology of Myositis in Rectal Cancer Patients Treated With Neoadjuvant Immune Checkpoint Inhibitors and Chemoradiotherapy: Findings From the CHINOREC Trial

Myositis is a rare (<1%) but potentially severe immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), with a 40%-50% fatality rate. Its incidence and pathology in curative, neoadjuvant settings, particularly with chemoradiotherapy (CRT), remain poorly defined. Given the severity, stringent diagnostic and therapeutic approaches may be warranted in curative patients. In the CHINOREC trial, 50 rectal cancer (RC) patients receiving neoadjuvant CRT with ipilimumab (IPI) and nivolumab (NIVO) were prospectively monitored for myotoxicity biomarkers, including creatine kinase (CK) and cardiac troponins (cTnT, cTnI). Patients with CK and cTnT levels above the upper limit normal with or without overt clinical symptoms underwent muscle biopsy and guideline-adapted treatment (glucocorticoids, immunoglobulin, infliximab, plasma exchange). Six patients (12%) developed biopsy-confirmed myositis. Elevated cTnT, but not cTnI, distinguished skeletal from cardiac involvement, aligning with normal cardiac magnetic resonance imaging (CMR) findings. Immunohistochemistry showed a predominant CD8+ T cell infiltrate and patchy human leukocyte antigen (HLA) Class I upregulation. Despite myositis, all patients underwent successful tumor resection with normalized CK levels and no residual cardiac dysfunction. ICI-induced myositis may be more frequent in neoadjuvant-treated RC patients receiving CRT+ICI than in palliative settings. Comprehensive biomarker monitoring and early T cell-directed intervention are essential for mitigating life-threatening irAEs while preserving oncologic outcomes.