{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:46:23Z","timestamp":1792406783716,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Older or medically unfit patients with newly diagnosed FLT3\u2010mutated acute myeloid leukemia (AML) have poor outcomes with hypomethylating agent (HMA) monotherapy. Venetoclax plus HMA is a modern lower\u2010intensity standard, but FLT3\u2010mutated AML remains biologically heterogeneous, and triplet regimens combining HMA, venetoclax, and a FLT3 inhibitor are increasingly used despite limited randomized comparative evidence. PubMed\/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, Scopus, and major hematology\/oncology conference proceedings were searched from inception to 12 June 2026 in accordance with PRISMA 2020 and MOOSE guidance. Eligible studies reported primary clinical outcomes for newly diagnosed FLT3\u2010ITD and\/or FLT3\u2010TKD AML treated with frontline lower\u2010intensity HMA alone, VEN\u2010HMA doublet, HMA\/LIC plus FLT3 inhibitor, or HMA\/LIC plus VEN plus FLT3 inhibitor therapy. Comparative effect estimates and single\u2010arm proportions were synthesized only when clinical and statistical assumptions were defensible. Thirteen eligible records were retained. Direct VEN\u00a0+\u00a0AZA versus AZA evidence came from one FLT3\u2010mutated pooled subgroup comparison (42 vs. 22 patients), showing CRc 67% versus 36%, RR 1.83 (95% CI 1.01\u20133.32), and median OS 12.5 versus 8.6\u00a0months. The randomized non\u2010venetoclax LACEWING trial showed higher CRc with gilteritinib\u00a0+\u00a0AZA than AZA (58.1% vs. 26.5%; HR for OS 0.916;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.753), illustrating that improved remission does not guarantee survival benefit. The principal comparative triplet evidence was one retrospective study: CR\/CRi 93% versus 70%, RR 1.32 (95% CI 1.09\u20131.61), with median OS not reached versus 9.5\u00a0months. Prospective and long\u2010term triplet reports described CR\/CRi rates of 93%\u201396%, deep FLT3\u2010ITD MRD negativity, and median OS up to 38.5\u00a0months; several reports derive from overlapping institutional series and non\u2010randomized designs, limiting independent corroboration and causal inference. VEN\u00a0+\u00a0AZA improves remission compared with AZA in the FLT3\u2010mutated subgroup, but the evidence base is underpowered for FLT3\u2010specific survival conclusions. Triplet therapy produces the strongest remission\u2010depth and MRD signals but has not shown superiority over VEN\u2010HMA in a randomized frontline comparison. On current evidence, triplets are a promising biologically rational strategy requiring direct randomized validation against the contemporary VEN\u2010HMA standard.\n                  <\/jats:p>","DOI":"10.1002\/hon.70257","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:45:56Z","timestamp":1790448356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Venetoclax\u2010Based Regimens in Newly Diagnosed FLT3\u2010Mutated Older or Unfit Acute Myeloid Leukemia: A Systematic Review and Meta\u2010Analysis of Comparative and Single\u2010Arm Outcomes"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9438-6589","authenticated-orcid":false,"given":"Mahboob Younus","family":"Shaik","sequence":"first","affiliation":[{"name":"Department of Internal Medicine CHI St. Vincent Hospital  Hot Springs Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Kaweah Health Medical Center  Visalia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishali","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Maharishi Markandeshwar Medical College and Hospital  Kumarhatti India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-1605","authenticated-orcid":false,"given":"Sunil","family":"Kakadia","sequence":"additional","affiliation":[{"name":"Genesis Cancer and Blood Institute  Hot Springs Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Divers","sequence":"additional","affiliation":[{"name":"Genesis Cancer and Blood Institute  Hot Springs Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010018\u20100357\u20109"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201001\u2010621664"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.9429"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201008\u2010868752"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012971"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003988"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201021\u20103405"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2015.02.017"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25198"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.263392"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014586"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010021\u201000410\u2010w"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010022\u201000670\u20100"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01911"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643\u20103230.BCD\u201024\u20100171"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2025.288553"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2026019841"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4919"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912\u2010023\u201001389\u20102"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6885"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024009"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35813"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon\u20102022\u20101286"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010025\u201002476\u20109"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010024\u201005891\u2010w"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010025\u201006543\u20103"},{"key":"e_1_2_13_31_1","unstructured":"BatallerA. 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