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Background The expansion of immune checkpoint inhibitors (ICIs) has transformed oncology globally, offering durable responses across multiple malignancies. 1 However, the rise in immune-related adverse events (irAEs), particularly grade ≥3 toxicities, introduces critical patient safety and health system challenges.2 South Asia, comprising India, Pakistan, Bangladesh, Sri Lanka, and Nepal, is experiencing the fastest projected rise in cancer incidence,3 yet under-reporting of ICI-related toxicities persists, highlighting access and monitoring gaps in the region.4 There is an urgent need for regional forecasting to guide preparedness. This study models the grade ≥3 irAE burden to 2035 across the region.Methods We focused on six ICI-approved malignancies: non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), melanoma, Hodgkin lymphoma, and head and neck squamous cell carcinoma (HNSCC). Incidence projections were sourced from GLOBOCAN 2020 [3], and population baselines from UN World Population Prospects. 5 Indian pharmaceutical utilization data informed logistic growth modeling under three adoption scenarios: conservative, baseline, and optimistic. Eligibility and irAE incidence rates were derived from meta-analyses.6 7 A 10,000-iteration Monte Carlo simulation was applied to propagate uncertainty. Resource requirements, including ICU admissions, ICU bed-days, corticosteroids, and endocrine support, were quantified using ASCO guidelines and South Asian ICU datasets.8 9 Results Baseline projections estimate 74,217 patients receiving ICIs in 2035—58,426 in India, 8,478 in Bangladesh, 6,500 in Pakistan, 1,026 in Sri Lanka, and 787 in Nepal. Lung and head and neck cancers account for over 65% of ICI-treated patients. Grade ≥3 irAEs are projected at 12,289 cases, with melanoma and RCC showing highest per-patient risks (30% and 25%, respectively). 6 This burden translates to 1,828 ICU admissions, 9,140 ICU bed-days, 12,300 steroid courses, and over 1,000 endocrine replacement cases8 9 (table 1). Sensitivity analysis shows that eligibility and uptake assumptions shift the treated population by ±25,000 and irAE counts by ±3,000. Under alternate scenarios, the irAE range spans 8,233–16,324 cases. Sankey and bar diagrams (figure 1) highlight India and Bangladesh as dominant contributors to toxicity and treatment burden.Conclusions By 2035, severe irAEs from ICIs may exceed 12,000 annually in South Asia, straining critical care systems. 8–10 Integrated irAE management within oncology pathways, expanded ICU infrastructure,10 multidisciplinary irAE clinics,11 and biosimilar harmonization are urgently needed. Dynamic real-world data registries will be essential for ongoing forecasting and policy adaptation.References Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–214. doi:10.1016/j.cell.2015.03.030Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721–1728. doi:10.1001/jamaoncol.2018.3923Ferlay J, Laversanne M, Ervik M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2020. Int J Cancer. 2021;149(3):778–789.Sinha P, Singh S, Agarwal P, et al. Under-reporting of ICI adverse drug reactions in VigiBase: South Asian perspective. Pharmacoepidemiol Drug Saf. 2023;32(10):1237–1245.United Nations, Department of Economic and Social Affairs. World Population Prospects. https://population.un.org/wpp/Wang PF, Chen Y, Song SY, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol. 2017;8:730. doi:10.3389/fphar.2017.00730Yoo WS, Ku EJ, Lee EK, et al. Incidence of endocrine-related dysfunction in patients treated with new immune checkpoint inhibitors: a meta-analysis and comprehensive review. Endocrinol Metab (Seoul). 2023;38(6):750–759. doi:10.3803/EnM.2023.1785Schneider BJ, Naidoo J, Santomasso BD, et al. ASCO guideline for management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy. J Clin Oncol. 2023;41(18):3973–4001.Toffart AC, Meert AP, Wallet F, et al. ICU admission for solid cancer patients treated with immune checkpoint inhibitors. Ann Intensive Care. 2023;13:55.Murthy S, Leligdowicz A, Adhikari NKJ. Intensive care unit capacity in low-income countries: a systematic review. PLoS One. 2015;10(1):e0116949.Khan SA, Kotha N, Tan CS, et al. Models of care for managing immune-related adverse events: the role of multidisciplinary irAE clinics. J Immunother Cancer. 2022;10(2):e003632.Abstract 1056 Table 1Projected ICI treatment volume and severe irAE-related resource needs in South Asia (2035 baseline scenario)Projected 2035 ICI-treated cases and associated healthcare burdens, including severe irAEs, ICU use, steroid therapy, and endocrine support, in five South Asian countries under the baseline adoption scenario.Abstract 1056 Figure 1Projected ICI-treated cases (blue) and severe irAEs (red) in South Asia under three uptake scenarios in 2035