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
Abstract Background 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...
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2021-08-01
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Series: | Journal of Hematology & Oncology |
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Online Access: | https://doi.org/10.1186/s13045-021-01142-x |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Farhad Ravandi Gail J. Roboz Andrew H. Wei Hartmut Döhner Christopher Pocock Dominik Selleslag Pau Montesinos Hamid Sayar Maurizio Musso Angela Figuera-Alvarez Hana Safah William Tse Sang Kyun Sohn Devendra Hiwase Timothy Chevassut Francesca Pierdomenico Ignazia La Torre Barry Skikne Rochelle Bailey Jianhua Zhong C. L. Beach Herve Dombret |
spellingShingle |
Farhad Ravandi Gail J. Roboz Andrew H. Wei Hartmut Döhner Christopher Pocock Dominik Selleslag Pau Montesinos Hamid Sayar Maurizio Musso Angela Figuera-Alvarez Hana Safah William Tse Sang Kyun Sohn Devendra Hiwase Timothy Chevassut Francesca Pierdomenico Ignazia La Torre Barry Skikne Rochelle Bailey Jianhua Zhong C. L. Beach Herve Dombret 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 Journal of Hematology & Oncology Oral azacitidine CC-486 Safety Maintenance |
author_facet |
Farhad Ravandi Gail J. Roboz Andrew H. Wei Hartmut Döhner Christopher Pocock Dominik Selleslag Pau Montesinos Hamid Sayar Maurizio Musso Angela Figuera-Alvarez Hana Safah William Tse Sang Kyun Sohn Devendra Hiwase Timothy Chevassut Francesca Pierdomenico Ignazia La Torre Barry Skikne Rochelle Bailey Jianhua Zhong C. L. Beach Herve Dombret |
author_sort |
Farhad Ravandi |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
Journal of Hematology & Oncology |
issn |
1756-8722 |
publishDate |
2021-08-01 |
description |
Abstract Background 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. Trial registration This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012. |
topic |
Oral azacitidine CC-486 Safety Maintenance |
url |
https://doi.org/10.1186/s13045-021-01142-x |
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doaj-643e4039c05b4d0693acd3685dcccc4b2021-08-29T11:03:42ZengBMCJournal of Hematology & Oncology1756-87222021-08-0114111410.1186/s13045-021-01142-xManagement of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trialFarhad Ravandi0Gail J. Roboz1Andrew H. Wei2Hartmut Döhner3Christopher Pocock4Dominik Selleslag5Pau Montesinos6Hamid Sayar7Maurizio Musso8Angela Figuera-Alvarez9Hana Safah10William Tse11Sang Kyun Sohn12Devendra Hiwase13Timothy Chevassut14Francesca Pierdomenico15Ignazia La Torre16Barry Skikne17Rochelle Bailey18Jianhua Zhong19C. L. Beach20Herve Dombret21Department of Leukemia, University of Texas MD Anderson Cancer CenterWeill Cornell MedicineDepartment of Clinical Haematology, The Alfred HospitalDepartment of Internal Medicine III, Ulm University HospitalKent & Canterbury HospitalAZ Sint-Jan Brugge-Oostende AVHospital Universitari i Politècnic La FeIndiana University Cancer CenterLa Maddalena - Casa di CuraHospital Universitario de La PrincesaTulane University Health Science CenterUniversity of Louisville School of MedicineKyungpook National University HospitalRoyal Adelaide HospitalBrighton and Sussex Medical SchoolPortuguese Institute of Oncology LisbonCelgene, a Bristol-Myers Squibb CompanyUniversity of Kansas Medical CenterBristol Myers SquibbBristol Myers SquibbBristol Myers SquibbHôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP)Abstract Background 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. Trial registration This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012.https://doi.org/10.1186/s13045-021-01142-xOral azacitidineCC-486SafetyMaintenance |