Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial

dc.contributor.authorRavandi, Farhad
dc.contributor.authorRoboz, Gail J.
dc.contributor.authorWei, Andrew H.
dc.contributor.authorDöhner, Hartmut
dc.contributor.authorPocock, Christopher
dc.contributor.authorSelleslag, Dominik
dc.contributor.authorMontesinos, Pau
dc.contributor.authorSayar, Hamid
dc.contributor.authorMusso, Maurizio
dc.contributor.authorFiguera‑Alvarez, Angela
dc.contributor.authorSafah, Hana
dc.contributor.authorTse, William
dc.contributor.authorSohn, Sang Kyun
dc.contributor.authorHiwase, Devendra
dc.contributor.authorChevassut, Timothy
dc.contributor.authorPierdomenico, Francesca
dc.contributor.authorLa Torre, Ignazia
dc.contributor.authorSkikne, Barry
dc.contributor.authorBailey, Rochelle
dc.contributor.authorZhong, Jianhua
dc.contributor.authorBeach, C. L.
dc.contributor.authorDombret, Herve
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2024-04-04T09:30:25Z
dc.date.available2024-04-04T09:30:25Z
dc.date.issued2021-08-28
dc.description.abstractBackground: Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors' clinical experience treating patients in the trial. Methods: QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. Results: A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1-80) oral azacitidine treatment cycles or 6 (1-73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3-4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications. Conclusion: Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy.
dc.eprint.versionFinal published version
dc.identifier.citationRavandi F, Roboz GJ, Wei AH, et al. Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial. J Hematol Oncol. 2021;14(1):133. Published 2021 Aug 28. doi:10.1186/s13045-021-01142-x
dc.identifier.urihttps://hdl.handle.net/1805/39745
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1186/s13045-021-01142-x
dc.relation.journalJournal of Hematology & Oncology
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectOral azacitidine
dc.subjectCC-486
dc.subjectSafety
dc.subjectMaintenance
dc.titleManagement of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial
dc.typeArticle
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