{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:36:10Z","timestamp":1791401770514,"version":"4.3.3"},"reference-count":35,"publisher":"American Society of Hematology","issue":"3","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,13]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>CD123, a subunit of the interleukin-3 receptor, is expressed on \u223c80% of acute myeloid leukemias (AMLs). Tagraxofusp (TAG), recombinant interleukin-3 fused to a truncated diphtheria toxin payload, is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm. We previously found that AMLs with acquired resistance to TAG were re-sensitized by the DNA hypomethylating agent azacitidine (AZA) and that TAG-exposed cells became more dependent on the antiapoptotic molecule BCL-2. Here, we report a phase 1b study in 56 adults with CD123-positive AML or high-risk myelodysplastic syndrome (MDS), first combining TAG with AZA in AML\/MDS, and subsequently TAG, AZA, and the BCL-2 inhibitor venetoclax (VEN) in AML. Adverse events with 3-day TAG dosing were as expected, without indication of increased toxicity of TAG or AZA+\/\u2212VEN in combination. The recommended phase 2 dose of TAG was 12\u00a0\u03bcg\/kg\/day for 3\u00a0days, with 7-day AZA\u00a0+\/\u2212 21-day VEN. In an expansion cohort of 26 patients (median age 71) with previously untreated European LeukemiaNet adverse-risk AML (50% TP53 mutated), triplet TAG-AZA-VEN induced response in 69% (n=18\/26; 39% complete remission [CR], 19% complete remission with incomplete count recovery [CRi], 12% morphologic leukemia-free state [MLFS]). Among 13 patients with TP53 mutations, 7\/13 (54%) achieved CR\/CRi\/MLFS (CR\u00a0= 4, CRi\u00a0= 2, MLFS\u00a0= 1). Twelve of 17 (71%) tested responders had no flow measurable residual disease. Median overall survival and progression-free survival were 14\u00a0months (95%\u00a0CI, 9.5-NA) and 8.5\u00a0months (95%\u00a0CI, 5.1-NA), respectively. In summary, TAG-AZA-VEN shows encouraging safety and activity in high-risk AML, including TP53-mutated disease, supporting further clinical development of TAG combinations. The study was registered on ClinicalTrials.gov as #NCT03113643.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/bloodadvances.2023011721","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T22:06:24Z","timestamp":1701813984000},"page":"591-602","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":53,"title":["Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia"],"prefix":"10.1182","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-0226","authenticated-orcid":false,"given":"Andrew A.","family":"Lane","sequence":"first","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-6302","authenticated-orcid":false,"given":"Jacqueline 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