PMID- 34454540
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20211101
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 14
IP  - 1
DP  - 2021 Aug 28
TI  - 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.
PG  - 133
LID - 10.1186/s13045-021-01142-x [doi]
LID - 133
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Ravandi, Farhad
AU  - Ravandi F
AUID- ORCID: 0000-0002-7621-377X
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, 1515 
      Holcombe Blvd., Houston, TX, 77030, USA. fravandi@mdanderson.org.
FAU - Roboz, Gail J
AU  - Roboz GJ
AD  - Weill Cornell Medicine, New York, NY, USA.
AD  - New York Presbyterian Hospital, New York, NY, USA.
FAU - Wei, Andrew H
AU  - Wei AH
AD  - Department of Clinical Haematology, The Alfred Hospital, Melbourne, Australia.
AD  - Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
FAU - Dohner, Hartmut
AU  - Dohner H
AD  - Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany.
FAU - Pocock, Christopher
AU  - Pocock C
AD  - Kent & Canterbury Hospital, Canterbury, UK.
FAU - Selleslag, Dominik
AU  - Selleslag D
AD  - AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium.
FAU - Montesinos, Pau
AU  - Montesinos P
AD  - Hospital Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Sayar, Hamid
AU  - Sayar H
AD  - Indiana University Cancer Center, Indianapolis, IN, USA.
FAU - Musso, Maurizio
AU  - Musso M
AD  - La Maddalena - Casa di Cura, Palermo, Italy.
FAU - Figuera-Alvarez, Angela
AU  - Figuera-Alvarez A
AD  - Hospital Universitario de La Princesa, Madrid, Spain.
FAU - Safah, Hana
AU  - Safah H
AD  - Tulane University Health Science Center, New Orleans, LA, USA.
FAU - Tse, William
AU  - Tse W
AD  - University of Louisville School of Medicine, Louisville, KY, USA.
FAU - Sohn, Sang Kyun
AU  - Sohn SK
AD  - Kyungpook National University Hospital, Daegu, Korea.
FAU - Hiwase, Devendra
AU  - Hiwase D
AD  - Royal Adelaide Hospital, Adelaide, Australia.
FAU - Chevassut, Timothy
AU  - Chevassut T
AD  - Brighton and Sussex Medical School, Brighton, UK.
FAU - Pierdomenico, Francesca
AU  - Pierdomenico F
AD  - Portuguese Institute of Oncology Lisbon, Lisbon, Portugal.
FAU - La Torre, Ignazia
AU  - La Torre I
AD  - Celgene, a Bristol-Myers Squibb Company, Boudry, Switzerland.
FAU - Skikne, Barry
AU  - Skikne B
AD  - University of Kansas Medical Center, Kansas City, KS, USA.
AD  - Bristol Myers Squibb, Princeton, NJ, USA.
FAU - Bailey, Rochelle
AU  - Bailey R
AD  - Bristol Myers Squibb, Princeton, NJ, USA.
FAU - Zhong, Jianhua
AU  - Zhong J
AD  - Bristol Myers Squibb, Princeton, NJ, USA.
FAU - Beach, C L
AU  - Beach CL
AD  - Bristol Myers Squibb, Princeton, NJ, USA.
FAU - Dombret, Herve
AU  - Dombret H
AD  - Hopital Saint-Louis, Assistance Publique - Hopitaux de Paris (AP-HP), Paris, 
      France.
AD  - Institut de Recherche Saint-Louis, Universite de Paris, Paris, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT01757535
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210828
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/chemically induced/therapy
MH  - Antimetabolites, Antineoplastic/administration & dosage/*adverse 
      effects/therapeutic use
MH  - Azacitidine/administration & dosage/*adverse effects/therapeutic use
MH  - Disease Management
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced/therapy
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neutropenia/chemically induced/therapy
MH  - Placebo Effect
MH  - Remission Induction
MH  - Thrombocytopenia/chemically induced/therapy
PMC - PMC8401338
OTO - NOTNLM
OT  - CC-486
OT  - Maintenance
OT  - Oral azacitidine
OT  - Safety
COIS- F.R. reports honoraria and consulting fees from Bristol Myers Squibb and Celgene; 
      and Research funding from Bristol Myers Squibb. G.J.R. reports Consultancy or 
      Advisory Board or Data and Safety Monitoring Committee: AbbVie, Actinium, Agios, 
      Amphivena, Amgen, Argenx, Array Biopharma, Astex, Astellas, AstraZeneca, Bayer, 
      Bristol Myers Squibb, Celgene, Celltrion, Daiichi Sankyo, Eisai, Epizyme, 
      GlaxoSmithKline, Helsinn, Janssen, Jasper Therapeutics, Jazz, Mesoblast, MEI 
      Pharma (IDMC Chair), Novartis, Orsenix, Otsuka, Pfizer, Roche/Genentech, Sandoz, 
      Takeda (IRC Chair), Trovagene; Research Support: Cellectis. A.H.W. reports 
      study-related fees and personal fees from Celgene; royalties from Walter and 
      Eliza Hall Institute of Medical Research; grants from the Medical Research Future 
      Fund; grants and personal fees from Servier, AbbVie, Novartis, Celgene, Astra 
      Zeneca, and Janssen; and personal fees from Astellas, Pfizer, Macrogenics, and 
      Amgen. H. Dohner reports personal fees from Abbvie, Agios, Astellas, Astex 
      Pharmaceuticals, Helsinn, Janssen, Oxford Biomedicals, and Roche; grants and 
      personal fees from Amgen, Celgene, Jazz Pharmaceuticals, and Novartis; and grants 
      from AROG Pharmaceuticals, Bristol Myers Squibb, Pfizer, and Sunesis. D.S. 
      reports honoraria from Novartis, Celgene, Amgen, Janssen-Cilag, AbbVie, Alexion, 
      GSK, MSD, Pfizer, Sanofi, Takeda, Incyte, and Teva; consultancy for Novartis, 
      Celgene, Amgen, Janssen-Cilag, AbbVie, Alexion, GSK, MSD, Pfizer, Sanofi, Takeda, 
      Incyte, and Teva; and speakers' bureau participation for Novartis, Celgene, 
      Amgen, MSD, Takeda, and Teva. P.M. reports Research support and advisory board by 
      Celgene-BMS. H.Sayar reports advisory board participation for BMS. H.Safah 
      reports speaker's bureau participation for Incyte, Celgene/BMS, Sanofi, 
      Karyopharm, and Amgen. D.H. reports research support from Celgene/BMS. H. Dombret 
      reports Research support and advisory board participation for Celgene-BMS. B.S., 
      R.B., J.Z., and C.L.B. are employed at and have equity ownership in Bristol Myers 
      Squibb. I.L.T. was formerly employed at Celgene, a Bristol-Myers Squibb Company, 
      and had equity ownership in Bristol Myers Squibb. C.P., M.M., A.F.-A., W.T., 
      S.K.S., and T.C. report no conflicts.
EDAT- 2021/08/30 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/08/28
CRDT- 2021/08/29 20:29
PHST- 2021/05/27 00:00 [received]
PHST- 2021/08/17 00:00 [accepted]
PHST- 2021/08/29 20:29 [entrez]
PHST- 2021/08/30 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/08/28 00:00 [pmc-release]
AID - 10.1186/s13045-021-01142-x [pii]
AID - 1142 [pii]
AID - 10.1186/s13045-021-01142-x [doi]
PST - epublish
SO  - J Hematol Oncol. 2021 Aug 28;14(1):133. doi: 10.1186/s13045-021-01142-x.