Evidence map›Paper›PMID 35960871›Full record

Trial reportBlood2022

Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine.

Hartmut Döhner, Andrew H Wei, Gail J Roboz, Pau Montesinos, Felicitas R Thol, Farhad Ravandi, Hervé Dombret, Kimmo Porkka, Irwindeep Sandhu, Barry Skikne and 7 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01757535 (A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia in Complete Remission), which is not on this map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01757535 phase3completednot on this map

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia in Complete Remission

TypeinterventionalSponsorCelgeneRan2013 to 2024Enrolled472ConditionsLeukemia, Myeloid, AcuteArmsOral Azacitidine, Placebo
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
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  3. Observational
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  6. Molecularly targeted therapy and immunotherapy in leukemias.Journal of hematology & oncology · 2026
    Review
  7. Article
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  18. MRD-directed and risk-adapted individualized stratified treatment of AML.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 10 institutions in 7 countries.

Hartmut DöhnerDepartment of Internal Medicine III, Ulm University Hospital, Ulm, Germany.ORCID 0000-0003-2116-5536
Andrew H WeiAustralian Centre for Blood Diseases, Monash University, Melbourne, Australia.ORCID 0000-0002-7514-3298
Gail J RobozHematology and Medical Oncology, Weill Cornell Medicine, New York, NY.ORCID 0000-0002-0384-3658
Pau MontesinosServicio de Hematología y Hemoterapia, Hospital Universitario y Politécnico La Fe, Valencia, Spain.ORCID 0000-0002-3275-5593
Felicitas R TholDepartment of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hannover, Germany.
Farhad RavandiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Hervé DombretLeukemia Unit, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Kimmo PorkkaHematology Research Unit Helsinki, HUS Comprehensive Cancer Center, and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-4112-5902
Irwindeep SandhuDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.ORCID 0000-0001-9407-6265
Barry SkikneUniversity of Kansas Medical Center, Kansas City, KS.
Wendy L SeeTranslational Medicine, Bristol Myers Squibb, Summit, NJ.
Manuel UgidosBMS Center for Innovation and Translational Research Europe (CITRE), a Bristol-Myers Squibb Company, Seville, Spain.
Alberto RisueñoBMS Center for Innovation and Translational Research Europe (CITRE), a Bristol-Myers Squibb Company, Seville, Spain.
Esther T ChanBristol Myers Squibb, Princeton, NJ.ORCID 0000-0002-2406-2623
Anjan ThakurtaTranslational Medicine, Bristol Myers Squibb, Summit, NJ.ORCID 0000-0003-0415-1706
C L BeachBristol Myers Squibb, Princeton, NJ.
Daniel Lopes de MenezesTranslational Medicine, Bristol Myers Squibb, Summit, NJ.
Bristol-Myers Squibb (United States) · USHospital Universitari i Politècnic La Fe · ESMedizinische Hochschule Hannover · DENewYork–Presbyterian Hospital · USThe Alfred Hospital · AUThe University of Texas MD Anderson Cancer Center · USUniversité Paris Cité · FRUniversity Hospital Ulm · DEUniversity of Alberta · CAUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial (ClinicalTrials.gov identifier: NCT01757535) evaluated oral azacitidine (Oral-AZA) in patients with acute myeloid leukemia (AML) in first remission after intensive chemotherapy (IC) who were not candidates for hematopoietic stem cell transplantation. Eligible patients were randomized 1:1 to Oral-AZA 300 mg or placebo for 14 days per 28-day cycle. We evaluated relapse-free survival (RFS) and overall survival (OS) in patient subgroups defined by NPM1 and FLT3 mutational status at AML diagnosis and whether survival outcomes in these subgroups were influenced by presence of post-IC measurable residual disease (MRD). Gene mutations at diagnosis were collected from patient case report forms; MRD was determined centrally by multiparameter flow cytometry. Overall, 469 of 472 randomized patients (99.4%) had available mutational data; 137 patients (29.2%) had NPM1 mutations (NPM1mut), 66 patients (14.1%) had FLT3 mutations (FLT3mut; with internal tandem duplications [ITD], tyrosine kinase domain mutations [TKDmut], or both), and 30 patients (6.4%) had NPM1mut and FLT3-ITD at diagnosis. Among patients with NPM1mut, OS and RFS were improved with Oral-AZA by 37% (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.98) and 45% (HR, 0.55; 95% CI, 0.35-0.84), respectively, vs placebo. Median OS was improved numerically with Oral-AZA among patients with NPM1mut whether without MRD (48.6 months vs 31.4 months with placebo) or with MRD (46.1 months vs 10.0 months with placebo) post-IC. Among patients with FLT3mut, Oral-AZA improved OS and RFS by 37% (HR, 0.63; 95% CI, 0.35-1.12) and 49% (HR, 0.51; 95% CI, 0.27-0.95), respectively, vs placebo. Median OS with Oral-AZA vs placebo was 28.2 months vs 16.2 months, respectively, for patients with FLT3mut and without MRD and 24.0 months vs 8.0 months for patients with FLT3mut and MRD. In multivariate analyses, Oral-AZA significantly improved survival independent of NPM1 or FLT3 mutational status, cytogenetic risk, or post-IC MRD status.

Indexed as

Leukemia, Myeloid, AcuteNuclear ProteinsAzacitidinefms-Like Tyrosine Kinase 3HumansMutationNeoplasm, ResidualNucleophosminPrognosisProtein-Tyrosine KinasesRecurrenceRemission InductionAzacitidineFLT3 protein, humanfms-Like Tyrosine Kinase 3Nuclear ProteinsNucleophosminProtein-Tyrosine Kinases

Identifiers

PMID35960871
PMCPMC10653004
OpenAlexW4290879107

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.