Oral Azacitidine (Oral-AZA) in Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC): Long-Term Overall Survival (OS) Results from the Phase 3 QUAZAR AML-001 Trial

November 2022 Vol 13, No 11 —November 17, 2022

Andrew H. Wei, MBBS, PhD1,2; Hartmut Döhner, MD3; Hamid Sayar, MD, MSc4; Farhad Ravandi, MBBS5; Pau Montesinos, MD, PhD6; Hervé Dombret, MD, PhD7,8; Dominik Selleslag, MD9; Kimmo Porkka, MD, PhD10,11; Jun Ho Jang, MD, PhD12; Barry Skikne, MD13,14; C.L. Beach, PharmD14; Yu (Olivia) Tian, PhD14; Gail J. Roboz, MD15,16

1Peter MacCallum Cancer Centre, Melbourne, Australia; 2Australian Centre for Blood Diseases, Monash University, Melbourne, Australia; 3Ulm University Hospital, Ulm, Germany; 4Indiana University Cancer Center, Indianapolis, IN, USA; 5The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6Hospital Universitario La Fe de Valencia, Valencia, Spain; 7Institut de Recherche Saint Louis, Université de Paris, Paris, France; 8Hôpital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France; 9AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium; 10iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland; 11Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; 12Samsung Medical Center, Seoul, Republic of Korea; 13University of Kansas Medical Center, Kansas City, KS, USA; 14Bristol Myers Squibb, Princeton, NJ, USA; 15Weil Cornell Medical College, New York, NY, USA; 16New York Presbyterian Hospital, New York, NY, USA

Background: For patients with AML in remission, navigating survivorship can be difficult; reduced contact with the treatment team and anxiety about disease relapse can cause significant distress. As such, it is important for members of the care team who support survivorship navigation to understand how active maintenance therapy with Oral-AZA might prolong remissions and OS for AML patients. In the randomized, phase-3 QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS vs placebo (median 24.7 vs 14.8 months, respectively; P <.001) in patients with AML in first remission after IC and ineligible for transplant. At the primary data cutoff (July 2019), more than one-quarter of all randomized patients (125/472 [26.5%]) were either still receiving Oral-AZA (n = 45) or placebo (n = 26), or remained alive in survival follow-up (n = 26 and n = 28). OS follow-up continued after the study was unblinded. We assessed longer-term survival for patients in QUAZAR AML-001 after >1 year of additional follow-up (September 2020).

Objective: To assess OS at an updated cutoff with additional follow-up.

Methods: Patients ≥55 years of age, with intermediate- or poor-risk cytogenetics at diagnosis and ECOG performance status ≤3, were randomized to Oral-AZA 300 mg or placebo once-daily for 14 days on a 28-day cycle within 4 months of first complete remission (CR)/CR with incomplete hematologic recovery (CRi). After unblinding, Oral-AZA–treated patients could continue treatment in an extension phase. OS was the time from randomization to death, consent withdrawal, or loss to follow-up. Baseline characteristics were compared for long-term (LT) survivors (alive ≥3 years from randomization) versus non-LT survivors.

Results: A total of 472 patients were randomized to Oral-AZA (n = 238) or placebo (n = 234). Median age was 68 years (range, 55-86), 91% of patients had de novo AML, and 86% had intermediate-risk cytogenetics. Upon trial unblinding, 39 (16%) Oral-AZA patients entered the extension phase. At the updated follow-up in September 2020, 54 (23%) Oral-AZA patients and 35 (15%) placebo patients were alive; 31 (13%) patients were still receiving Oral-AZA. At a median follow-up of 51.7 months, median OS in each arm remained unchanged (24.7 vs 14.8 months; P = .0008). However, Kaplan-Meier curves showed greater separation at later time points and did not overlap. Kaplan-Meier–

estimated 3-year OS rate was 37.4% with Oral-AZA vs 27.9% with placebo (∆ +9.5% [95% CI, 0.9-18.1]).

Compared with non-LT survivors, LT survivors (n = 140; 83 Oral-AZA, 57 placebo) were more likely to have intermediate-risk cytogenetics (95% vs 82%) and NPM1mut (45% vs 23%) at AML diagnosis, and less likely to have measurable residual disease (MRD) post-IC (33% vs 52%). Among patients with post-IC MRD, 71% (34/48) of LT survivors became MRD– on study, compared with 15% (26/172) of non-LT survivors (P <.0001).

Conclusions: Updated survival data from QUAZAR AML-001 showed a sustained, long-term survival ben-

efit with Oral-AZA. Intermediate-risk cytogenetics and NPM1mut at diagnosis, and absence of post-IC MRD, were associated with long-term survival. Oral-AZA offers a promising alternative to prolonging remission and survival when transplant is not an option. These data may inform patient navigators when identifying patients with AML in remission who can benefit from Oral-AZA to improve health outcomes.

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Last modified: August 10, 2023

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