{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:10:08Z","timestamp":1747149008302,"version":"3.40.5"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parsaclisib is a potent and highly selective PI3K\u03b4 inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R\/R) follicular lymphoma (FL). CITADEL\u2010102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R\/R FL. Patients were \u226518\u00a0years of age with histologically confirmed and documented CD20\u2010positive FL, and R\/R to previous rituximab\u2010containing treatment regimens. Part one (safety run\u2010in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open\u2010label, single\u2010group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty\u2010six patients were enrolled in CITADEL\u2010102 and all patients received parsaclisib 20\u00a0mg once daily for 8\u00a0weeks, followed by 20\u00a0mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run\u2010in experienced a dose\u2010limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment\u2010emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty\u2010three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL\u2010102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R\/R FL who progressed following prior rituximab\u2010containing regimens.<\/jats:p>","DOI":"10.1002\/hon.3209","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T05:44:41Z","timestamp":1690436681000},"page":"848-857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL\u2010102): A phase 1 study"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5372-510X","authenticated-orcid":false,"given":"Mehdi","family":"Hamadani","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morton","family":"Coleman","sequence":"additional","affiliation":[{"name":"Clinical Research Alliance Inc.  Westbury New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Boccia","sequence":"additional","affiliation":[{"name":"Center for Cancer and Blood Disorders  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juraj","family":"Duras","sequence":"additional","affiliation":[{"name":"Department of Haematooncology University Hospital Ostrava and Faculty of Medicine University of Ostrava  Ostrava Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hutchings","sequence":"additional","affiliation":[{"name":"Department of Haematology and Phase 1 Unit Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-2651","authenticated-orcid":false,"given":"Pier Luigi","family":"Zinzani","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna Istituto di Ematologia \u201cSer\u00e0gnoli\u201d  Bologna Italy"},{"name":"Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Universit\u00e0 di Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul","family":"Cordoba","sequence":"additional","affiliation":[{"name":"Lymphoma Unit Department of Hematology Fundaci\u00f3n Jimenez Diaz University Hospital  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Bastos","family":"Oreiro","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Williams","sequence":"additional","affiliation":[{"name":"Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Stouffs","sequence":"additional","affiliation":[{"name":"Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Langmuir","sequence":"additional","affiliation":[{"name":"Incyte Corporation  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-6538","authenticated-orcid":false,"given":"Juan\u2010Manuel","family":"Sancho","sequence":"additional","affiliation":[{"name":"Clinical Hematology Department Institut Catal\u00e0 d'Oncologia\u2010Hospital Germans Trias i Pujol, IJC  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100132\u2010x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000317"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx189"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.21037\/aol\u201021\u20101"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.11.008"},{"key":"e_1_2_10_7_1","unstructured":"National Comprehensive Cancer Network.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): B\u2010Cell Lymphomas.https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/b\u2010cell.pdf. 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