PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have become the standard of care for stage IV non–small cell lung cancer (NSCLC). In 2021, Lebanon experienced a severe economic collapse that resulted in major shortages of immunotherapy and treatment interruptions. The aim of this study was to explore the potential impact of immunotherapy shortage on progression-free survival (PFS). METHODS: This retrospective multicenter study included patients with newly diagnosed stage IV NSCLC treated between January 2019 and December 2020 (control group) and between October 2021 and December 2022 (crisis group). The primary end point was PFS, defined from treatment initiation to progression according to RECIST 1.1 criteria or death. Kaplan-Meier survival curves were generated, and differences were assessed using log-rank test. RESULTS: A total of 500 medical records were reviewed; 158 eligible patients were included (73 control, 85 crisis). The total cohort included 60.8% men with a mean age of 69.7 years. Among immunotherapy recipients, 44.0% received full-dose therapy (dose density ratio = 1.0), 41.4% received 50%-99% of standard dose (dose density ratio = 0.50-0.99), and 14.7% received <50% (dose density ratio = <0.50). The median PFS was 6.33, 12.86, and 10.23 months, respectively; no statistically significant difference was observed ( P = .132). CONCLUSION: Despite a statistically significant reduction in immunotherapy dose density during the economic crisis, no statistically significant difference in PFS was detected between the precrisis and crisis groups. These findings suggest that reduced immunotherapy dosing may not be associated with inferior short-term survival outcomes in stage IV NSCLC, although the study was not designed or powered to establish equivalence.

Background/Objectives: Immune checkpoint inhibitors have revolutionized the treatment of advanced melanoma, yet primary and acquired resistance remain major barriers to durable disease control. This narrative review examines the clinical patterns, biological mechanisms, biomarker limitations, and therapeutic implications of immunotherapy failure. Methods: A structured search of PubMed, Web of Science, and ClinicalTrials.gov identified relevant studies published from January 2010 to May 2026, supplemented by landmark earlier reports. Results: Immunotherapy resistance encompasses heterogeneous patterns, including early progression, oligoprogression, dissociated response, brain-dominant progression, relapse after response, and progression after treatment discontinuation. These clinical phenotypes arise from overlapping mechanisms such as loss of antigen presentation, impaired interferon signaling, oncogenic immune exclusion, melanoma dedifferentiation, suppressive myeloid and regulatory T-cell programs, stromal and vascular barriers, metabolic restriction, and deterioration of tumor-reactive T-cell clones. Conventional response criteria and static biomarkers, including PD-L1 expression and tumor mutational burden, do not adequately capture this complexity because resistance varies across lesions and evolves under treatment pressure. Negative trials of IDO1 inhibition, cytokine intensification, vaccines, and intratumoral immune stimulation further show that biological plausibility and early activity do not guarantee clinical benefit when target engagement, patient enrichment, and endpoint selection are inadequate. Conclusions: Immunotherapy resistance in melanoma should be viewed as a variety of biologically distinct clinical states rather than a single endpoint. Future progress will require resistance-matched treatment, longitudinal tissue and circulating tumor DNA assessment, adaptive trial designs, and endpoints aligned with treatment kinetics. This framework may improve salvage selection and interpretation of post-PD-1 studies in clinical practice.