Background and PurposeNeoadjuvant immunotherapy currently significantly enhances treatment efficacy for locally advanced rectal cancer (LARC); However, clinical management of immune-related adverse events (irAEs) lacks robust evidence. This study aimed to investigate the characteristics, clinical management strategies, and outcomes of irAEs during neoadjuvant immunotherapy for rectal cancer, providing a basis for optimizing irAEs monitoring and intervention.MethodsWe retrospectively analyzed clinical data from LARC patients who developed irAEs after receiving neoadjuvant immunotherapy at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, between July 2022 and June 2024. Types of irAEs, severity, time of onset, management strategies, and outcomes were recorded. All patients underwent regular follow-up for at least 6 months. This study has been approved by Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (ethical approval number: I-24PJ0024). Descriptive statistics were used to summarize irAEs patterns and management approaches.ResultsA total of 41 irAE episodes occurred among the 30 patients. Mild irAEs (Grade 1-2) accounted for 78.0% (32/41), while severe irAEs (Grade 3-4) constituted 22.0% (9/41). Five patients (16.7%) permanently discontinued treatment due to severe toxicity. Endocrine toxicities were most frequent (36.6%, 15/41), primarily characterized by progression from hyperthyroidism to hypothyroidism; 75.0% required thyroid hormone replacement therapy. One case of delayed-onset adrenal insufficiency was alleviated with glucocorticoid (GC) therapy. Among hepatotoxicities (19.5%, 8/41), 62.5% were Grade 3 injury, and 37.5% required GC intervention; two patients experienced recurrence during adjuvant chemotherapy. Three cases of severe myositis occurred, accompanied by asymptomatic myocardial injury (evidenced by markedly elevated creatine kinase and concurrent changes in cardiac biomarkers), all requiring high-dose GC pulse therapy combined with intravenous immunoglobulin or immunosuppressants (recovery period: 2-4 months). Nine dermatological reactions were managed with topical therapy. Two gastrointestinal events occurred, including one Grade 3 diarrhea treated with GCs. The overall GC usage rate was 31.7% (13/41), with 76.9% administered for Grade ≥3 irAEs.ConclusionirAEs during neoadjuvant immunotherapy for LARC are predominantly mild-to-moderate and manageable with supportive care. However, some patients develop severe (Grade 3-4) irAEs requiring multidisciplinary management. GC usage is concentrated in highergrade irAEs, with severe myositis and cardiac involvement necessitating intensive immunosuppressive therapy despite their rarity. Recurrence of irAEs during adjuvant chemotherapy in a minority of patients underscores the necessity for early recognition, graded intervention, and comprehensive management throughout the entire treatment cycle.