Abstract 3214: The duration of immune checkpoint inhibitors (ICI) in oncology: Longer is not better

Abstract ICI addition to the oncology armamentarium provided significant therapeutic benefits. Standard schedule of ICI calls for 2-year regimen without rational justification. Doses selected clearly do not adhere to classic maximal tolerated dose since ICIs were doubled at longer dose intervals. Theoretically however, multiple concerns can be proposed to question the 2-year duration. In human neoadjuvant melanoma studies examining ICI effect on effector T-cells comprehensively documented the expected clonal expansion in target cells but this was noted only for few weeks and did not continue upon repeated dosing, a major challenge to the current standard dosing schedule. Therapeutic T-cell transfers administer a single dose of 109 , a bulk that is expected to require 2-3 weeks of lymphocyte proliferation. Neutralizing antibodies have been reported in multiple studies, but notably without detriment to the therapeutic impact. Lastly, published and unpublished cases confirm lasting benefits (in years) after single ICI dosing. We hypothesized that benefits of ICI depend mostly, if not entirely, on the first, or few initial doses; that doses later in time can be delivered but add little if anything to the therapeutic impact. Methods/Results: we reviewed published ICI monotherapy or chemo-ICI which provided individual swimmers’ plot in stage 4 melanoma, renal cell and NSCLC. We extracted the median survival (MS) of those who received variable ICI durations excluding progression as the cause for halting therapy. Patients with progressive disease beyond 6 months, were included because they received considerable durations of ICI and might enjoy lasting benefits. We report the MS in the times depicted in the table. Our data reveal comparable results in all subgroups supporting our hypothesis. Conclusions: Despite standard recommendations, there is considerable rationale in addition to our current data to challenge the common duration of ICI and substantiate a far more limited exposure to ICI. Table ICI Duration Median Survival (Months) Number of Cases 1-3 months 27 29 3-6 months 31.5 24 6-12 months 32 63 12-18 months 35 30 18-24 months 37 47 24+ months 48 32 Citation Format: Farah Mazahreh, Samuel L. Schach, Liyan Mazahreh, A. Mazin Safar. The duration of immune checkpoint inhibitors (ICI) in oncology: Longer is not better [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3214.