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CLINICAL AND BIOLOGICAL MARKERS ASSOCIATED WITH LONG-TERM SURVIVAL FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) IN REMISSION AFTER CHEMOTHERAPY IN THE QUAZAR AML-001 TRIAL OF ORAL AZACITIDINE
Author(s): ,
Andrew H. Wei
Affiliations:
Department of Clinical Haematology,Alfred Hospital, and the Australian Centre for Blood Diseases, Monash University,Melbourne,Australie;Department of Clinical Haematology,Alfred Hospital, and the Australian Centre for Blood Diseases, Monash University,Melbourne,Australien;Department of Clinical Haematology,Alfred Hospital, and the Australian Centre for Blood Diseases, Monash University,Melbourne,A
,
Hartmut Döhner
Affiliations:
Department of Internal Medicine III,Ulm University Hospital,Ulm,Allemagne;Department of Internal Medicine III,Ulm University Hospital,Ulm,Deutschland;Department of Internal Medicine III,Ulm University Hospital,Ulm,Germania;Department of Internal Medicine III,Ulm University Hospital,Ulm,Germany;Department of Internal Medicine III,Ulm University Hospital,Ulm,Alemania;Department of Internal Medicine
,
Hamid Sayar
Affiliations:
Indiana University Cancer Center,Indianapolis,États-unis;Indiana University Cancer Center,Indianapolis,Vereinigte Staaten;Indiana University Cancer Center,Indianapolis,Stati Uniti;Indiana University Cancer Center,Indianapolis,United States;Indiana University Cancer Center,Indianapolis,Estados Unidos;Indiana University Cancer Center,Indianapolis,Verenigde Staten;Indiana University Cancer Center,Ind
,
Farhad Ravandi
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,États-unis;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States;Department of Leukem
,
Pau Montesinos
Affiliations:
Hospital Universitario y Politécnico La Fe,Valencia,Espagne;Hospital Universitario y Politécnico La Fe,Valencia,Spanien;Hospital Universitario y Politécnico La Fe,Valencia,Spagna;Hospital Universitario y Politécnico La Fe,Valencia,Spain;Hospital Universitario y Politécnico La Fe,Valencia,España;Hospital Universitario y Politécnico La Fe,Valencia,Spanje;Hospital Universitario y Politécnico La Fe,Va
,
Hervé Dombret
Affiliations:
Hematology, Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), and Institut de Recherche Saint-Louis, Université de Paris,Paris,France;Hematology, Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), and Institut de Recherche Saint-Louis, Université de Paris,Paris,Frankreich;Hematology, Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), and In
,
Dominik Selleslag
Affiliations:
AZ Sint-Jan Brugge-Oostende AV,Bruges,Belgique;AZ Sint-Jan Brugge-Oostende AV,Bruges,Belgien;AZ Sint-Jan Brugge-Oostende AV,Bruges,Belgio;AZ Sint-Jan Brugge-Oostende AV,Bruges,Belgium;AZ Sint-Jan Brugge-Oostende AV,Bruges,Bélgica;AZ Sint-Jan Brugge-Oostende AV,Bruges,België;AZ Sint-Jan Brugge-Oostende AV,Bruges,Bélgica;AZ Sint-Jan Brugge-Oostende AV,Bruges,Belgium;AZ Sint-Jan Brugge-Oostende AV,Br
,
Kimmo Porkka
Affiliations:
HUS Comprehensive Cancer Center, Hematology Research Unit Helsinki and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki,Helsinki,Finlande;HUS Comprehensive Cancer Center, Hematology Research Unit Helsinki and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki,Helsinki,Finnland;HUS Comprehensive Cancer Center, Hematology Research Unit Helsin
,
Jun-Ho Jang
Affiliations:
Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Corée, République De;Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Corea del Sud;Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,South Korea,Republic;Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Zuid Korea;Samsung Medical Center, Sungkyunkwan Univ
,
Barry Skikne
Affiliations:
Bristol Myers Squibb,Princeton,États-unis;Bristol Myers Squibb,Princeton,Vereinigte Staaten;Bristol Myers Squibb,Princeton,Stati Uniti;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,Verenigde Staten;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,USA
,
CL Beach
Affiliations:
Bristol Myers Squibb,Princeton,États-unis;Bristol Myers Squibb,Princeton,Vereinigte Staaten;Bristol Myers Squibb,Princeton,Stati Uniti;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,Verenigde Staten;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,USA
,
Thomas Prebet
Affiliations:
Bristol Myers Squibb,Princeton,États-unis;Bristol Myers Squibb,Princeton,Vereinigte Staaten;Bristol Myers Squibb,Princeton,Stati Uniti;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,Verenigde Staten;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,USA
,
George Zhang
Affiliations:
Bristol Myers Squibb,Princeton,États-unis;Bristol Myers Squibb,Princeton,Vereinigte Staaten;Bristol Myers Squibb,Princeton,Stati Uniti;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,Verenigde Staten;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,USA
,
Alberto Risueño
Affiliations:
BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol-Myers Squibb Company),Seville,Espagne;BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol-Myers Squibb Company),Seville,Spanien;BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol-Myers Squibb Company),Seville,Spagna;BMS Center for Innovation and Translational Research
,
Manuel Ugidos Guerrero
Affiliations:
BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol-Myers Squibb Company),Seville,Espagne;BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol-Myers Squibb Company),Seville,Spanien;BMS Center for Innovation and Translational Research Europe (CITRE, a Bristol-Myers Squibb Company),Seville,Spagna;BMS Center for Innovation and Translational Research
,
Wendy L. See
Affiliations:
Bristol Myers Squibb,Princeton,États-unis;Bristol Myers Squibb,Princeton,Vereinigte Staaten;Bristol Myers Squibb,Princeton,Stati Uniti;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,Verenigde Staten;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,USA
,
Daniel Menezes
Affiliations:
Bristol Myers Squibb,Princeton,États-unis;Bristol Myers Squibb,Princeton,Vereinigte Staaten;Bristol Myers Squibb,Princeton,Stati Uniti;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,Verenigde Staten;Bristol Myers Squibb,Princeton,Estados Unidos;Bristol Myers Squibb,Princeton,United States;Bristol Myers Squibb,Princeton,USA
Gail J. Roboz
Affiliations:
Weill Cornell Medicine and New York Presbyterian Hospital,New York,États-unis;Weill Cornell Medicine and New York Presbyterian Hospital,New York,Vereinigte Staaten;Weill Cornell Medicine and New York Presbyterian Hospital,New York,Stati Uniti;Weill Cornell Medicine and New York Presbyterian Hospital,New York,United States;Weill Cornell Medicine and New York Presbyterian Hospital,New York,Estados U
(Abstract release date: 05/12/22) EHA Library. H. Wei A. 06/10/22; 357361; P498
Andrew H. Wei
Andrew H. Wei
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P498

Type: Poster presentation

Session title: Acute myeloid leukemia - Clinical

Background
In the randomized, phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA) significantly prolonged overall survival (OS) compared with placebo (PBO) (median OS 24.7 vs 14.8 months [mo], respectively) in older patients (pts) with AML in first remission after intensive chemotherapy (IC). At an updated data cutoff performed in Sep 2020, 34.9% of pts in the Oral-AZA arm and 24.4% of pts in the PBO arm remained alive at ≥3 y from randomization.

Aims
Assess clinical and biological variables associated with long-term survival (LTS) in QUAZAR AML-001.

Methods
In all, 472 pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO QD ×14d/28d within 4 mo of achieving first complete remission (CR) or CR with incomplete blood count recovery (CRi) after IC. The primary endpoint was OS, time from randomization until death, withdrawal of consent, or loss to follow-up. The LTS cohort comprised pts who were alive ≥3 y from randomization as of Sep 2020 and the non-LTS cohort included pts who died or were censored before 3 y. Variables assessed for association with LTS were diagnostic (Dx [pre-IC]) features (AML subtype, cytogenetic risk, NPM1 and FLT3 mutations [mut]); pre-study treatment (Tx) variables (response to IC [CR/CRi], receipt of consolidation, number of consolidation cycles); baseline (BL) demographic and disease characteristics, hematologic parameters (red blood cells [RBCs], hemoglobin, platelets, and leukocyte subsets), and measurable residual disease (MRD) status; and post-BL variables (MRD response [conversion from MRD+ at BL to MRD– on study], timing of MRD– [MRD– response on-study vs BL MRD–], and receipt of transplant after Tx discontinuation [D/C]). Associations of LTS with bone marrow immune parameters (CD3, CD4, and CD8 T-cell counts, and expression of PD-1/TIM-3 T-cell exhaustion markers) were investigated in a subset of pts (n=108). Variables were compared within Tx arms (LTS vs non-LTS) in univariate analyses with P values corrected for multiple testing. A logistic multivariable regression analysis of the effects of prognostic BL covariates on LTS was performed.

Results
The LTS cohort included 83/238 pts (34.9%) in the Oral-AZA arm and 57/234 pts (24.4%) in the PBO arm. Within both arms, factors significantly associated with LTS were intermediate (Int)-risk cytogenetics and NPM1mut at Dx, and MRD response (MRD+ to MRD–) on study (Figure). MRD response rate was 2-fold higher with Oral-AZA vs PBO (37% vs 19%, respectively), and while early attrition was more common in the PBO arm, most MRD responses occurred within 6 mo. Factors significantly associated with LTS only in the PBO arm were BL (post-IC) MRD– status and receipt of transplant after Tx D/C. No significant associations were observed between BL hematological or immune parameters and LTS.

The multivariable analysis (MVA) confirmed Oral-AZA Tx as independently significantly predictive of LTS vs PBO. Other covariates significantly associated with LTS in MVA were Int-risk cytogenetics and NPM1mut at Dx, and MRD– status at BL.

Conclusion
Oral-AZA Tx was significantly associated with LTS vs PBO. In univariate analysis, Int-risk cytogenetics and NPM1mut at Dx, and MRD response on-study, were significantly prognostic of LTS in both arms, whereas MRD– status at BL (post-IC) was associated with LTS only in the PBO arm.

Keyword(s): AML, Azacitidine, Long-term follow-up, Maintenance

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P498

Type: Poster presentation

Session title: Acute myeloid leukemia - Clinical

Background
In the randomized, phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA) significantly prolonged overall survival (OS) compared with placebo (PBO) (median OS 24.7 vs 14.8 months [mo], respectively) in older patients (pts) with AML in first remission after intensive chemotherapy (IC). At an updated data cutoff performed in Sep 2020, 34.9% of pts in the Oral-AZA arm and 24.4% of pts in the PBO arm remained alive at ≥3 y from randomization.

Aims
Assess clinical and biological variables associated with long-term survival (LTS) in QUAZAR AML-001.

Methods
In all, 472 pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO QD ×14d/28d within 4 mo of achieving first complete remission (CR) or CR with incomplete blood count recovery (CRi) after IC. The primary endpoint was OS, time from randomization until death, withdrawal of consent, or loss to follow-up. The LTS cohort comprised pts who were alive ≥3 y from randomization as of Sep 2020 and the non-LTS cohort included pts who died or were censored before 3 y. Variables assessed for association with LTS were diagnostic (Dx [pre-IC]) features (AML subtype, cytogenetic risk, NPM1 and FLT3 mutations [mut]); pre-study treatment (Tx) variables (response to IC [CR/CRi], receipt of consolidation, number of consolidation cycles); baseline (BL) demographic and disease characteristics, hematologic parameters (red blood cells [RBCs], hemoglobin, platelets, and leukocyte subsets), and measurable residual disease (MRD) status; and post-BL variables (MRD response [conversion from MRD+ at BL to MRD– on study], timing of MRD– [MRD– response on-study vs BL MRD–], and receipt of transplant after Tx discontinuation [D/C]). Associations of LTS with bone marrow immune parameters (CD3, CD4, and CD8 T-cell counts, and expression of PD-1/TIM-3 T-cell exhaustion markers) were investigated in a subset of pts (n=108). Variables were compared within Tx arms (LTS vs non-LTS) in univariate analyses with P values corrected for multiple testing. A logistic multivariable regression analysis of the effects of prognostic BL covariates on LTS was performed.

Results
The LTS cohort included 83/238 pts (34.9%) in the Oral-AZA arm and 57/234 pts (24.4%) in the PBO arm. Within both arms, factors significantly associated with LTS were intermediate (Int)-risk cytogenetics and NPM1mut at Dx, and MRD response (MRD+ to MRD–) on study (Figure). MRD response rate was 2-fold higher with Oral-AZA vs PBO (37% vs 19%, respectively), and while early attrition was more common in the PBO arm, most MRD responses occurred within 6 mo. Factors significantly associated with LTS only in the PBO arm were BL (post-IC) MRD– status and receipt of transplant after Tx D/C. No significant associations were observed between BL hematological or immune parameters and LTS.

The multivariable analysis (MVA) confirmed Oral-AZA Tx as independently significantly predictive of LTS vs PBO. Other covariates significantly associated with LTS in MVA were Int-risk cytogenetics and NPM1mut at Dx, and MRD– status at BL.

Conclusion
Oral-AZA Tx was significantly associated with LTS vs PBO. In univariate analysis, Int-risk cytogenetics and NPM1mut at Dx, and MRD response on-study, were significantly prognostic of LTS in both arms, whereas MRD– status at BL (post-IC) was associated with LTS only in the PBO arm.

Keyword(s): AML, Azacitidine, Long-term follow-up, Maintenance

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