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

Dominik Selleslag¹  Timothy Chevassut²  Rochelle Bailey³  C. L. Beach³  Jianhua Zhong³  Ignazia La Torre⁴  Andrew H. Wei⁵  Hartmut Döhner⁶  Farhad Ravandi⁷  Pau Montesinos⁸  Angela Figuera-Alvarez⁹  Herve Dombret^1,10  Hamid Sayar^1,11  Christopher Pocock^1,12  Sang Kyun Sohn^1,13  Maurizio Musso^1,14  Francesca Pierdomenico^1,15  Devendra Hiwase^1,16  Hana Safah^1,17  Barry Skikne^1,18  William Tse^1,19  Gail J. Roboz^2,20 

[1] AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium;Brighton and Sussex Medical School, Brighton, UK;Bristol Myers Squibb, Princeton, NJ, USA;Celgene, a Bristol-Myers Squibb Company, Boudry, Switzerland;Department of Clinical Haematology, The Alfred Hospital, Melbourne, Australia;Australian Centre for Blood Diseases, Monash University, Melbourne, Australia;Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany;Department of Leukemia, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA;Hospital Universitari i Politècnic La Fe, Valencia, Spain;Hospital Universitario de La Princesa, Madrid, Spain;Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France;Institut de Recherche Saint-Louis, Université de Paris, Paris, France;Indiana University Cancer Center, Indianapolis, IN, USA;Kent & Canterbury Hospital, Canterbury, UK;Kyungpook National University Hospital, Daegu, Korea;La Maddalena - Casa di Cura, Palermo, Italy;Portuguese Institute of Oncology Lisbon, Lisbon, Portugal;Royal Adelaide Hospital, Adelaide, Australia;Tulane University Health Science Center, New Orleans, LA, USA;University of Kansas Medical Center, Kansas City, KS, USA;Bristol Myers Squibb, Princeton, NJ, USA;University of Louisville School of Medicine, Louisville, KY, USA;Weill Cornell Medicine, New York, NY, USA;New York Presbyterian Hospital, New York, NY, USA;

关键词: Oral azacitidine;    CC-486;    Safety;    Maintenance;   

DOI  :  10.1186/s13045-021-01142-x

来源: Springer

【 摘 要 】

BackgroundMost 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.MethodsQUAZAR 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.ResultsA 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.ConclusionOral 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.

【 授权许可】

CC BY