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A prior study showed that about a quarter of melanoma patients who responded to PD-1–blockade therapy with pembrolizumab had disease progression at a median follow-up of 21 months (NEJM JW Oncol Hematol Jul 2016 and JAMA 2016; 315:1600). To determine genetic mechanisms of acquired resistance to PD-1–blockade therapy, investigators analyzed biopsy samples from metastatic melanoma patients who experienced progression after an initial response.
Of 78 patients, 42 had objective clinical responses, and 15 of the responders progressed. Of the responders who progressed, 4 qualified for the study, since they had responses lasting more than 6 months (progression-free survival, 13–29 months), and they provided sufficient tissue before treatment and at…