Retrospective cohort study of neoadjuvant immune checkpoint inhibitors for dMMR/MSI-H gastroesophageal adenocarcinoma

A retrospective cohort study at the Mayo Clinic evaluated clinical outcomes with neoadadjuvant immune checkpoint inhibitors (nICIs) for deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) gastroesophageal adenocarcinoma (GEA), with a focus on the feasibility of nonoperative management (NOM). From institutional records, 26 patients treated between 2017 and 2025 were identified. Nine patients (34.6%) underwent surgery, of whom six (66.7%) achieved pathologic complete response. Seventeen patients (65.4%) pursued NOM, with 10 of 14 evaluable patients (71.4%) achieving clinical complete response. One patient who initially achieved clinical complete response had a local recurrence on surveillance endoscopy and underwent salvage endoscopic resection. At a median follow-up of 19.3 montsh, 15 of 17 patients (88.2%) in the NOM cohort were alive and metastasis-free, with EFS rates of 87.3% at 12 and 24 months for all patients. Immune-related adverse events occurred in 34.6% of patients, with no grade ≥ 3 toxicities.The authors conclude that in this retrospective cohort study, nICIs led to high complete response rates in dMMR/MSI-H GEA, supporting the feasibility of NOM in select patients.