The efficacy of immune checkpoint inhibitors (ICI) in ALK-positive non small-cell lung cancer (NSCLC) is inconclusive as a result of limited data. We conducted a real-world analysis in 83 patients with ALK(+) advanced NSCLC treated with ICI. The median real-world progression-free survival was 2.34 months from initiation of ICI therapy. The real-world effectiveness of ICI in ALK(+) NSCLC patients was limited. Introduction: The treatment landscape for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) primarily involves ALK-directed tyrosine kinase inhibitors (TKIs). Although therapy with immune checkpoint inhibitors (ICIs) is a treatment option in NSCLC, the efficacy of ICI is inconclusive in ALK-positive NSCLC as a result of limited data. This retrospective real-world study sought to describe the characteristics of ALK-positive NSCLC patients treated with ICI and to assesses treatment outcomes in US oncology practices. Patients and Methods: This analysis used the Flatiron Health electronic health record-derived deidentified database and included adult (18 years and older) ALK-positive advanced NSCLC patients with receipt of one or more ICIs after January 1, 2015. Median time to ICI discontinuation and real-world progression-free survival (rwPFS) were estimated by Kaplan-Meier methods. Results: Of 83 patients with ALK-positive NSCLC treated with ICIs, 50.6% (n = 42) received ICI without a prior ALK TKI. Median time to ICI discontinuation was 2.17 months (95% confidence interval, 1.41, 3.32). The median rwPFS was 2.34 months (95% confidence interval, 1.55, 3.09); in patients who received an ICI without prior ALK TKI, it was 3.9 months, and in patients who received ICI therapy after an ALK TKI, it was 1.5 months. Conclusions: Real-world effectiveness (rwPFS) of ICIs in ALK-positive NSCLC patients, whether provided before or after TKIs, was limited, underscoring the relative lack of efficacy of ICI in this patient population, particularly compared to approved ALK TKIs. (C) 2020 The Authors. Published by Elsevier Inc.