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RESEARCH PRODUCT
Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort.
Amir T. FathiPau MontesinosGail J. RobozThomas PrebetThomas CluzeauSarah PerreaultSteven D. GoreAndrew M. BrunnerJosefina SerranoRami S. KomrokjiPierre FenauxVey NorbertNikolai A. PodoltsevRaphael ItzyksonVivek VermaMark R. LitzowMichelle DeveauxAmer M. ZeidanJohn BarnardVijaya Raj BhattEllen K. RitchieJuan BerguaUlrich GermingAref Al-kaliMikkael A. SekeresTae Kon KimMaximilian StahlValeria Santinisubject
0301 basic medicineAdultmedicine.medical_specialtyAntimetabolites AntineoplasticMyeloidAdolescentDatabases FactualAzacitidineDecitabineSalvage therapyDecitabineCohort Studies03 medical and health sciencesYoung Adult0302 clinical medicineRefractoryInternal medicinehemic and lymphatic diseasesmedicineHumansSurvival analysisAgedRetrospective StudiesAged 80 and overSalvage TherapyMyeloid Neoplasiabusiness.industryRemission InductionRetrospective cohort studyHematologyDNA MethylationMiddle Agedmedicine.diseasePrognosisSurvival AnalysisLeukemiaLeukemia Myeloid Acute030104 developmental biologymedicine.anatomical_structureTreatment Outcome030220 oncology & carcinogenesisAdolescent; Adult; Aged; Aged 80 and over; Antimetabolites Antineoplastic; Cohort Studies; DNA Methylation; Databases Factual; Decitabine; Humans; Leukemia Myeloid Acute; Middle Aged; Prognosis; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Analysis; Treatment Outcome; Young Adultbusinessmedicine.drugdescription
Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment–refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-04-23 |