Real-world evidence of lower-dose intensity of immune checkpoint inhibitors in MSI-H/dMMR gastrointestinal cancers from a resource-constrained setting

Background: Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in metastatic microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) gastrointestinal (GI) malignancies. However, in fragile settings, especially in low- and middle-income countries (LMIC) and areas of conflict, access remains severely limited by prohibitive costs and supply chain disruptions. Starting in late 2019, Lebanon's economic crisis led to health system collapse, currency devaluation, medication shortages, and ongoing conflict, which necessitated adaptive treatment strategies. Early pharmacodynamic studies suggest lower ICI doses may achieve comparable efficacy; however, real-world evidence from conflict-affected settings where dose reductions occur by necessity rather than design remains absent. This study examines ICI dosing outcomes during Lebanon's acute crisis period. Methods: We conducted a retrospective analysis of adult patients with metastatic MSI-H/dMMR GI cancers treated with ICIs at the American University of Beirut Medical Center between 2018 and 2024, encompassing Lebanon's economic collapse and acute health system fragility. Dose-intensity was calculated as the percentage of actual dose received compared to the recommended dose. Patients were stratified into