Improving Accessibility and Affordability of Immune Checkpoint Inhibitors using Markedly Lower Doses at Reduced Frequency

Immune checkpoint inhibitors (ICIs), specifically agents blocking the programmed death-1 (PD-1) protein and its ligand (PD-L1), have revolutionized cancer therapy by offering durable responses and favorable toxicity profiles across a broad spectrum of malignancies.However, their widespread adoption at a global level remains severely limited by high costs, which particularly affect their accessibility and affordability in low-and-middle-income countries (LMICs).This review explores emerging strategies to optimize ICI dosing-specifically, low-dose (LD) and reduced-frequency dosing (RFD)-to enhance global accessibility and affordability, while maintaining clinical efficacy.We summarize pharmacokinetic and pharmacodynamic evidence supporting the biological efficacy of LD and RFD dosing strategies of ICIs.Emerging data from several clinical studies further validate these two strategies, demonstrating comparable outcomes to standard regimens.We also discuss the rationale for combining the LD and RFD approaches, which could significantly lower treatment costs, maintain clinical efficacy, enhance patient convenience, and enable the safe extension of immunotherapy over multiple years.We also introduce the AFFORD-IO (Attenuated Frequency and Reduced Dose of Immuno-Oncology treatment) trial, a first-of-its-kind study in sub-Saharan Africa, evaluating a novel combined LD plus RFD regimen of nivolumab in ICI-responsive cancers.Adoption of such a regimen could lead to marked reduction in the cost of ICI therapy and hence, transform cancer care delivery in both resource-constrained and resource-abundant settings, offering a powerful tool against the rapidly increasing global cancer burden.binaytara.org/