{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:43:14Z","timestamp":1785253394480,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T00:00:00Z","timestamp":1535673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002686","name":"Vera Bradley Foundation for Breast Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duvelisib (IPI\u2010145) is an oral dual inhibitor of phosphoinositide\u20103\u2010kinase (PI3K)\u2010\u03b4 and \u2010\u03b3 in clinical development for the treatment of hematologic malignancies, including indolent non\u2010Hodgkin lymphoma (iNHL). In a Phase 1, open\u2010label study to determine the maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, clinical activity, and safety of duvelisib monotherapy in patients with advanced hematologic malignancies, duvelisib was administered at eight dose levels (8\u2010100\u2009mg BID) in a dose\u2010escalation phase (<jats:italic>n<\/jats:italic> =\u200931 evaluable patients). Two dose\u2010limiting toxicities (DLTs), Grade 3 transaminase elevations and Grade 3 rash, occurred at 100\u2009mg BID, and the MTD was determined to be 75\u2009mg BID. Across all doses, 58.1% of iNHL patients had a response (19.4% complete, 35.5% partial, and 3.2% minor); median time to response was 1.84\u2009months and duration of response was 16.9 months. Median progression\u2010free survival was 14.7 months, and the probability of overall survival at 24\u2009months was 71.7%. Severe (Grade\u2009\u2265 3) adverse events included elevated liver enzymes (38.7%), diarrhea (25.8%), and neutropenia (29.0%). Three patients, all in the 75\u2009mg BID cohort, experienced fatal AEs: <jats:italic>E. coli<\/jats:italic> sepsis, acute respiratory failure, and fungal pneumonia. No iNHL patients experienced <jats:italic>Pneumocystis<\/jats:italic> pneumonia. Duvelisib demonstrated favorable clinical activity and an acceptable safety profile in these high\u2010risk, heavily pretreated, relapsed\/refractory iNHL patients, with 25\u2009mg BID selected for further clinical development.<\/jats:p>","DOI":"10.1002\/ajh.25228","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T06:25:52Z","timestamp":1532327152000},"page":"1311-1317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Duvelisib, an oral dual PI3K\u2010\u03b4, \u03b3 inhibitor, shows clinical activity in indolent non\u2010Hodgkin lymphoma in a phase 1 study"],"prefix":"10.1002","volume":"93","author":[{"given":"Ian W.","family":"Flinn","sequence":"first","affiliation":[{"name":"Sarah Cannon Research Institute  Nashville Tennessee"},{"name":"Tennessee Oncology  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Patel","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute  Nashville Tennessee"},{"name":"Florida Cancer Specialists  Sarasota Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Oki","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Horwitz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francine F.","family":"Foss","sequence":"additional","affiliation":[{"name":"Yale University Cancer Center  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Allen","sequence":"additional","affiliation":[{"name":"Infinity Pharmaceuticals, Inc.  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