{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T05:10:28Z","timestamp":1734412228212,"version":"3.30.2"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32HL007093"],"award-info":[{"award-number":["T32HL007093"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The tumor microenvironment (TME), including infiltrating T\u2010cells, is thought to play a major role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to its widely varied disease course. We hypothesized that programmed death\u20101 inhibition may be most effective in untreated, immunocompetent FL patients. Thus, we developed a phase 2 study to evaluate the efficacy of pembrolizumab as the initial treatment for indolent B\u2010cell lymphoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adults with FL or marginal zone lymphoma and an indication for treatment were eligible. Patients received pembrolizumab 200\u00a0mg IV in 21\u2010day cycles for up to 18 cycles, until progression or unacceptable toxicity. Early response assessment was obtained after cycle 3 with computed tomography (CT), and a fluorodeoxyglucose (FDG)\u2010positron emission tomography\u2010computed tomography (PET\u2010CT) was obtained after cycle 6 to determine candidacy for continuation in the study. Immunosecretome profiling was performed at baseline and on cycle 2 day 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine patients with FL were enrolled between February 2019 and April 2021, including eight (89%) with advanced stage, seven (78%) with intermediate\/high Follicular Lymphoma International Prognostic Index, and six (67%) with high\u2010tumor burden by Groupe d'Etude des Lymphomes Folliculaires. The best overall response rate by FDG PET\u2010CT was 33% (three partial metabolic responses). Three patients (33%) had stable disease, and three (33%) had progressive disease (including one patient who only had a follow\u2010up CT). By CT four (44%) experienced a reduction in target lesions, but all were less than partial responses. Grade 3 or higher immune\u2010related adverse events (IRAEs) were seen in two (22%) patients, both with transaminitis and one of whom had concurrent hypophysitis. Another patient had grade 1 pneumonitis, requiring treatment with steroids. No associations between the immunosecretome profile and clinical outcomes could be detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Frontline pembrolizumab for FL is associated with limited responses and a clinically significant rate of IRAEs. Alternative strategies for targeting the TME in FL should be explored.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jha2.1029","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T13:34:03Z","timestamp":1728567243000},"page":"1173-1181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase 2 study of frontline pembrolizumab in follicular lymphoma"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-9377","authenticated-orcid":false,"given":"Carrie","family":"Ho","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine University of Washington  Seattle Washington USA"},{"name":"Clinical Research Division Fred Hutchinson Cancer Center  Seattle Washington 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