{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:40:11Z","timestamp":1792431611210,"version":"4.5.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>In randomized studies, addition of FLT3 inhibitors failed to improve survival in older patients with FLT3-ITD AML unfit for intensive chemotherapy. Although hypomethylating agents or low-dose cytarabine combined with venetoclax is standard, FLT3-ITD is an important mechanism of resistance and a barrier to improved survival. Recent studies show promise for the addition of gilteritinib or quizartinib to less intensive venetoclax-based therapy, however resulting marrow toxicity requires substantial reductions to administered treatment. The INTERVENE study (Investigating Novel Triplets to Extend Remission with VENetoclax in Elderly AML) (ACTRN12619001655134) examined the role of midostaurin (M) administered sequentially after low-dose cytarabine (L) combined with venetoclax (V) in patients with newly diagnosed AML \u226560 years with non-adverse karyotype. After a run-in phase (n=18) established that LDAC combined with venetoclax from days 1-28 and midostaurin from days 11-28 was tolerable, 120 patients were randomized 2:1 to receive either LVM or LV. For the primary endpoint, LVM did not improve composite complete remission (CRc), compared to LV (72% vs 68%). Combining midostaurin with LV enhanced CRc among the sub-group of patients (n=29) with FLT3-ITD (82% vs 57%, difference = 25%, 0.85 posterior probability true difference &amp;gt; 5%, 95% CrI: -10 to 59%) and improved FLT3-ITD clearance as measured by ultrasensitive NGS (65% vs 0%), resulting in longer OS (median 24.2 vs 8.8 months, HR=0.34, 95% CrI: 0.071 to 0.960), compared to LV. In conclusion, midostaurin combined with low-dose cytarabine and venetoclax is well-tolerated and may have a role in newly diagnosed FLT3-ITD AML unfit for intensive chemotherapy.<\/jats:p>","DOI":"10.1182\/blood.2026035389","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:04:33Z","timestamp":1792429473000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["A randomized phase 2 study combining midostaurin, low-dose cytarabine and venetoclax in newly diagnosed AML \u226560 years"],"prefix":"10.1182","author":[{"given":"Chong Chyn","family":"Chua","sequence":"first","affiliation":[{"name":"Monash Health and Monash University, Rosanna, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hsun Hsun","family":"Hsu","sequence":"additional","affiliation":[{"name":"Christchurch Hospital, Christchurch, New Zealand, Christchurch, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop K.","family":"Enjeti","sequence":"additional","affiliation":[{"name":"University of Newcastle, Newcastle, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Bajel","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Marlton","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun A","family":"Fleming","sequence":"additional","affiliation":[{"name":"Alfred Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6666-3056","authenticated-orcid":false,"given":"Devendra K.","family":"Hiwase","sequence":"additional","affiliation":[{"name":"Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-kei-kris Kris","family":"Ma","sequence":"additional","affiliation":[{"name":"Westmead Hospital, Westmead, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Browett","sequence":"additional","affiliation":[{"name":"The University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2788-9893","authenticated-orcid":false,"given":"Carolyn S.","family":"Grove","sequence":"additional","affiliation":[{"name":"Sir Charles Gairdner Hospital\/PathWest, Nedlands, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShuhYing","family":"Tan","sequence":"additional","affiliation":[{"name":"St. Vincent's Hospital, Fitzroy, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Perera","sequence":"additional","affiliation":[{"name":"Wellington Hospital, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jad","family":"Othman","sequence":"additional","affiliation":[{"name":"Royal North Shore Hospital and Faculty of Medicine and Health, The University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Rose","sequence":"additional","affiliation":[{"name":"University Hospital Geelong, Geelong, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian P","family":"Cooney","sequence":"additional","affiliation":[{"name":"Fiona Stanley Hospital, Murdoch, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward S","family":"Morris","sequence":"additional","affiliation":[{"name":"The Townsville Hospital, Townsville, QL, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"McCulloch","sequence":"additional","affiliation":[{"name":"NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Mason","sequence":"additional","affiliation":[{"name":"Australasian Leukaemia and Lymphoma Group, Richmond, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1627-8934","authenticated-orcid":false,"given":"Rachel M","family":"Koldej","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Johnston","sequence":"additional","affiliation":[{"name":"Westmead Hospital, Westmead, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7755-8326","authenticated-orcid":false,"given":"Stephen B","family":"Ting","sequence":"additional","affiliation":[{"name":"Eastern Health-Monash University, Box Hill, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre and Royal Melboure Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-1403","authenticated-orcid":false,"given":"Natasha S","family":"Anstee","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8825-8625","authenticated-orcid":false,"given":"John","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Alfred Health and Monash University, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-3298","authenticated-orcid":false,"given":"Andrew H","family":"Wei","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2026,10,19]]},"container-title":["Blood Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2026035389\/2595842\/blood.2026035389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2026035389\/2595842\/blood.2026035389.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:04:34Z","timestamp":1792429474000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2026035389\/571625\/A-randomized-phase-2-study-combining-midostaurin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2026035389","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"article-number":"blood.2026035389"}}