Adaptive immunotherapy dosing in cancer: a structured narrative review and conceptual framework for future clinical investigation

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but approved schedules do not establish whether treatment intensity should remain constant as tumor burden, immunity, toxicity, and response evolve. Continued treatment after durable response may add toxicity and treatment burden while providing uncertain incremental benefit. This structured narrative review examines adaptive immunotherapy dosing: prespecified, state-dependent modification of dose, interval, or duration, including interruption and resumption. Exposure–response plateaus and time-varying clearance support investigating alternative regimens but do not establish clinical equivalence. Evidence on discontinuation remains disease- and regimen-specific, precluding generalization from melanoma to non-small cell lung cancer or other settings. Response- and biomarker-guided strategies have prospective support in defined settings, including response-driven adjuvant therapy in melanoma and circulating tumor DNA–selected adjuvant therapy in muscle-invasive bladder cancer. These advances do not validate repeated biomarker-guided adjustment of ICI dose, interval, or duration. Most candidate longitudinal biomarkers show outcome associations without demonstrated utility for dosing adaptation. Artificial intelligence and computational models may integrate serial data but require prospective evaluation, external validation, and safeguards against unsafe individual predictions. Dynamic treatment regimes and adaptive trial methods offer tools for evaluating complete policies, with attention to endpoints, patient preferences, assay performance, equity, and regulation. The proposed conceptual framework organizes these requirements for prospective investigation; it is not a clinical algorithm. Trials must establish whether matching treatment intensity to an evolving clinical state preserves efficacy while reducing toxicity and burden and improving quality of life. Approved regimens and validated disease-specific strategies remain the clinical benchmark.