{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:35:28Z","timestamp":1790760928659,"version":"4.1.0"},"reference-count":45,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"35","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,12,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed\/refractory FLT3-mutated ( FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      ) acute myeloid leukemia (AML) but seldom reduces FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      burden or induces sustained efficacy. Gilteritinib combines synergistically with the BCL-2 inhibitor venetoclax in preclinical models of FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      AML.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      This phase Ib open-label, dose-escalation\/dose-expansion study (ClinicalTrials.gov identifier: NCT03625505 ) enrolled patients with FLT3 wild-type and FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      (escalation) or FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      (expansion) relapsed\/refractory AML. Patients received 400 mg oral venetoclax once daily and 80 mg or 120 mg oral gilteritinib once daily. The primary objectives were safety, identification of the recommended phase II dose, and the modified composite complete response (mCRc) rate (complete response [CR] + CR with incomplete blood count recovery + CR with incomplete platelet recovery + morphologic leukemia-free state) using ADMIRAL phase III\u2013defined response criteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Sixty-one patients were enrolled (n = 56 FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      ); 64% (n = 36 of 56) of FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      patients had received prior FLT3 inhibitor therapy. The recommended phase II dose was 400 mg venetoclax once daily and 120 mg gilteritinib once daily. The most common grade 3\/4 adverse events were cytopenias (n = 49; 80%). Adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively. The mCRc rate for FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      patients was 75% (CR, 18%; CR with incomplete blood count recovery, 4%; CR with incomplete platelet recovery, 18%; and morphologic leukemia-free state, 36%) and was similar among patients with or without prior FLT3 inhibitor therapy (80% v 67%, respectively). The median follow-up was 17.5 months. The median time to response was 0.9 months, and the median remission duration was 4.9 months (95% CI, 3.4 to 6.6). FLT3 molecular response (&lt; 10\n                      <jats:sup>\u22122<\/jats:sup>\n                      ) was achieved in 60% of evaluable mCRc patients (n = 15 of 25). The median overall survival for FLT3\n                      <jats:sup>mut<\/jats:sup>\n                      patients was 10.0 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The combination of venetoclax and gilteritinib was associated with high mCRc and FLT3 molecular response rates regardless of prior FLT3 inhibitor exposure. Dose interruptions were needed to mitigate myelosuppression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.22.00602","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T16:01:11Z","timestamp":1658160071000},"page":"4048-4059","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":200,"title":["Venetoclax Plus Gilteritinib for\n                    <i>FLT3<\/i>\n                    -Mutated Relapsed\/Refractory Acute Myeloid Leukemia"],"prefix":"10.1200","volume":"40","clinical-trial-number":[{"clinical-trial-number":"nct03625505","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-373X","authenticated-orcid":false,"given":"Naval","family":"Daver","sequence":"first","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-2231","authenticated-orcid":false,"given":"Alexander E.","family":"Perl","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Maly","sequence":"additional","affiliation":[{"name":"Department of Hematologic Malignancies and Cellular Therapy, Norton Cancer Institute, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Levis","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9816-6302","authenticated-orcid":false,"given":"Mark","family":"Litzow","sequence":"additional","affiliation":[{"name":"Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McCloskey","sequence":"additional","affiliation":[{"name":"Department of Leukemia, John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-7026","authenticated-orcid":false,"given":"Catherine C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Schiller","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Miami, Miami, FL"},{"name":"Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon V.","family":"Tiu","sequence":"additional","affiliation":[{"name":"Astellas Pharma US, Northbrook, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Naqvi","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-8829","authenticated-orcid":false,"given":"Monique","family":"Dail","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna","family":"Brackman","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya","family":"Siddani","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-9696","authenticated-orcid":false,"given":"Brenda","family":"Chyla","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lee","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-1896","authenticated-orcid":false,"given":"Jessica K.","family":"Altman","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000115"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-020-00765-5"},{"key":"b3","first-page":"124","volume":"10","author":"Brandwein JM","year":"2020","journal-title":"Am J Blood Res"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018016121"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.52.8562"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00201-6"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1011"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902688"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716984"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-04-779405"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00495-3"},{"key":"b12","first-page":"1911","volume":"10","author":"Nakao M","year":"1996","journal-title":"Leukemia"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.8.2434"},{"key":"b14","first-page":"6766","volume":"18","author":"Tao S","year":"2019","journal-title":"Oncol Lett"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.25"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1752"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.23"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30416-3"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000919"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.7514"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3652"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018015925"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.03011"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-136395"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614359"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00964-5"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018029496"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-402545"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-06-1978"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1453"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012971"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020004856"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0313"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.244020"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00973-4"},{"key":"b36","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0832"},{"key":"b37","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00578-4"},{"key":"b38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544"},{"key":"b39","volume-title":"Venetoclax [package insert]","year":"2021"},{"key":"b40","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.036"},{"key":"b41","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00888-w"},{"key":"b42","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.821"},{"key":"b43","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.03345"},{"key":"b44","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26447"},{"key":"b45","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00410-w"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.22.00602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T18:00:20Z","timestamp":1670436020000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.22.00602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,10]]},"references-count":45,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2022,12,10]]}},"alternative-id":["10.1200\/JCO.22.00602"],"URL":"https:\/\/doi.org\/10.1200\/jco.22.00602","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,10]]},"assertion":[{"value":"2022-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-28","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}