{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:10:29Z","timestamp":1785179429383,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Myeloid neoplasms (myelodysplastic syndrome [MDS], myelofibrosis, and chronic myelomonocytic [CMML]) are aggressive hematological malignancies for which, despite recent approvals, novel therapies are needed to improve clinical outcomes. The hedgehog (HH) pathway is one of the main pathways for cancer stem cells survival and several HH inhibitors (HHi) are approved in clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sonidegib (SON), an oral HHi, was tested in this phase 1\/1b trial in combination with azacitidine (AZA, 75\u00a0mg\/m<jats:sup>2<\/jats:sup> days \u00d77) in patients with newly diagnosed and relapsed\/refractory (r\/r) chronic MN or acute myeloid leukemia (AML).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010two patients (28 [45%] newly diagnosed) were treated in this study, including 10 patients in the dose\u2010finding component and 52 patients in phase 1b. SON 200\u00a0mg oral daily on days 1\u201328 each cycle was deemed the recommended dose for phase 1b. Out of 21 rrAML patients, two achieved response (one complete response\/one morphologic leukemia\u2010free state) with no responses seen in seven r\/r MDS\/CMML patients. In newly diagnosed AML\/MDS, response was seen in six (three had complete remission, two had morphological leukemia\u2010free status) of 27 patients. Median overall survival was 26.4 and 4.7\u00a0months for newly diagnosed MDS and AML, respectively. Safety was satisfactory with common (&gt;20%) side effects including fatigue, constipation, nausea, cough, insomnia, and diarrhea. Only 7% of patients died in the study, and none of the deaths were deemed related to treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study shows that AZA\u00a0+\u00a0SON are a safe combination in a patient with MN. Similar to other hedgehog inhibitors, this combination yielded limited response rate in patients with myeloid neoplasms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34800","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:44:00Z","timestamp":1681267440000},"page":"2321-2330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phase 1\/1b study of azacitidine and hedgehog pathway inhibitor sonidegib in patients with myeloid neoplasms"],"prefix":"10.1002","volume":"129","author":[{"given":"Raoul","family":"Tibes","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi E.","family":"Kosiorek","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  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