{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:05:01Z","timestamp":1786964701098,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T00:00:00Z","timestamp":1682121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002975","name":"Dainippon Sumitomo Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Relapsed\/refractory (R\/R) Acute Myeloid Leukemia (AML) is a genetically complex and heterogeneous disease with a poor prognosis and limited treatment options. Thus, there is an urgent need to develop therapeutic combinations to overcome drug resistance in AML. This open\u2010label, multicenter, international, phase 1b study evaluated the safety, efficacy, and pharmacokinetics of venetoclax in combination with alvocidib in patients with R\/R AML. Patients were treated with escalating doses of venetoclax (400, 600, and 800\u00a0mg QD, orally, days 1\u201328) and alvocidib (45 and 60\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , intravenously, days 1\u20133) in 28\u2010day cycles. The combination was found to be safe and tolerable, with no maximum tolerated dose reached. Drug\u2010related Grade \u22653 adverse events were reported in 23 (65.7%) for venetoclax and 24 (68.6%) for alvocidib. No drug\u2010related AEs were fatal. Gastrointestinal toxicities, including diarrhea, nausea, and vomiting were notable and frequent; otherwise, the toxicities reported were consistent with the safety profile of both agents. The response rate was modest (complete remission [CR]\u00a0+\u00a0incomplete CR [CRi], 11.4%; CR\u00a0+\u00a0CRi\u00a0+\u00a0partial response rate\u00a0+\u00a0morphologic leukemia\u2010free state, 20%). There was no change in alvocidib pharmacokinetics with increasing doses of venetoclax. However, when venetoclax was administered with alvocidib, AUC\n                    <jats:sub>24<\/jats:sub>\n                    and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    decreased by 18% and 19%, respectively. A recommended phase 2 dose was not established due to lack of meaningful increase in efficacy across all cohorts compared to what was previously observed with each agent alone. Future studies could consider the role of the sequence, dosing, and the use of a more selective MCL1 inhibitor for the R\/R AML population.\n                  <\/jats:p>","DOI":"10.1002\/hon.3159","type":"journal-article","created":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T14:39:30Z","timestamp":1682174370000},"page":"743-752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A phase 1b study of venetoclax and alvocidib in patients with relapsed\/refractory acute myeloid leukemia"],"prefix":"10.1002","volume":"41","author":[{"given":"Brian A.","family":"Jonas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Division of Malignant Hematology, Cell Therapy and Transplantation University of California Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Zhou","family":"Hou","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center Cancer Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail J.","family":"Roboz","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine and New York\u2010Presbyterian Hospital  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline L.","family":"Alvares","sequence":"additional","affiliation":[{"name":"Department of Haematology University Hospital of Wales  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8822-1814","authenticated-orcid":false,"given":"Deepa","family":"Jeyakumar","sequence":"additional","affiliation":[{"name":"Chao Comprehensive Cancer Center University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Indiana Blood and Marrow Transplantation  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry P.","family":"Erba","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Haematology St. James's University Hospital  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"R\u00f6llig","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum TU  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Fiedler","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-4554","authenticated-orcid":false,"given":"Deanna","family":"Brackman","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  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