Immune checkpoint inhibitors (ICIs) have redefined the therapeutic landscape of oncology, producing durable responses across multiple tumor types and treatment settings. However, widespread adoption of ICIs has introduced challenges related to cost, optimal dosing, treatment duration, and immune-related toxicities, particularly in low- and middle-income countries (LMICs), where resource constraints have driven pragmatic innovations in delivery. This review summarizes exposure optimization strategies, including low-dose regimens, extended-interval dosing, fixed-duration therapy, and biomarker-guided patient selection supported by pharmacokinetic and pharmacodynamic data showing near-maximal PD-1 receptor occupancy at lower doses. Clinical evidence from randomized trials and real-world studies across tumor types suggest that these approaches may preserve efficacy in selected settings while improving affordability and feasibility. These LMIC-driven adaptations in treatment delivery, toxicity surveillance, and health-system design offer practical insights that may be applicable to high-resource settings facing sustainability challenges. Importantly, exposure optimization strategies have direct implications for toxicity burden, particularly immune-related adverse events (irAEs), hence the manuscript also reviews key organ-specific irAEs, with a focus on cardiovascular and gastrointestinal toxicities, emphasizing early detection, multidisciplinary management, and the relationship between treatment intensity and toxicity burden. Together, these approaches represent an attempt to improve the scalability of immunotherapy while balancing effectiveness, safety, and cost across different health care settings.
Trikha et al. (Thu,) studied this question.