{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:04:17Z","timestamp":1788537857631,"version":"build-2803163510"},"reference-count":26,"publisher":"American Society of Hematology","issue":"5","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"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":[[2025,1,30]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Glutamine dependency has been shown to be a metabolic vulnerability in acute myeloid leukemia (AML). Prior studies using several in\u00a0vivo AML models showed that depletion of plasma glutamine, induced by long-acting crisantaspase (pegcrisantaspase [PegC]) was synergistic with the B-cell lymphoma-2 (BCL-2) inhibitor venetoclax (Ven), resulting in significantly reduced leukemia burden and enhanced survival. Here, we report a phase 1 study of the combination of Ven and PegC (VenPegC) for treating adult patients with relapsed or refractory AML, including patients who had previously received Ven. The primary end points were the incidence of regimen-limiting toxicities (RLTs) and the maximum tolerated dose (MTD). Twenty-five patients received at least 1 PegC dose with Ven, and 18 efficacy-evaluable patients completed at least 1 VenPegC cycle; 12 (67%) had previously received Ven. Hyperbilirubinemia was the RLT and occurred in 60% of patients treated with VenPegC; 20% had grade \u22653 bilirubin elevations. MTD was determined to be Ven 400 mg daily with biweekly PegC 750 IU\/m2. The most common treatment-related adverse events of any grade in 25 patients who received VenPegC included antithrombin III decrease (52%), elevated transaminases (36%-48%), fatigue (28%), and hypofibrinogenemia (24%). No thromboembolic or hemorrhagic adverse events or clinical pancreatitis were observed. The overall complete remission rate in efficacy-evaluable patients was 33%. Response correlated with alterations in proteins involved in messenger RNA translation. In patients with RUNX1 mutations, the composite complete remission rate was 100%. This study was registered at www.ClinicalTrials.gov as #NCT04666649.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024024837","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T22:01:49Z","timestamp":1729634509000},"page":"486-496","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":11,"title":["A phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed or refractory acute myeloid leukemia"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-3257","authenticated-orcid":false,"given":"Yuchen","family":"Liu","sequence":"first","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD"},{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, 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G.","family":"Lapidus","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD"},{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Baer","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD"},{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9254-0095","authenticated-orcid":false,"given":"Sandrine","family":"Niyongere","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD"},{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0278-7727","authenticated-orcid":false,"given":"Vu H.","family":"Duong","sequence":"additional","affiliation":[{"name":"1Division of Hematology\/Oncology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD"},{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine C.","family":"Dougherty","sequence":"additional","affiliation":[{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8978-9401","authenticated-orcid":false,"given":"Jan H.","family":"Beumer","sequence":"additional","affiliation":[{"name":"4Cancer Therapeutics Program, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA"},{"name":"5Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA"},{"name":"6Division of Hematology\/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine D.","family":"Caprinolo","sequence":"additional","affiliation":[{"name":"2University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4169-7978","authenticated-orcid":false,"given":"Farin","family":"Kamangar","sequence":"additional","affiliation":[{"name":"7Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, 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