Real World Outcomes of Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia: A Single Center Experience

Introduction: About 50% of patients with acute myeloid leukemia (AML) relapse after achieving complete remission (CR). Maintenance therapy in AML aims to prolong the overall survival (OS) of patients by relapse prevention. In the QUAZAR AML-001 study, oral azacitidine (Oral-AZA) showed significantly longer OS (24.7 vs. 14.8 months) and relapse-free-survival (RFS) (10.2 vs. 4.8 months) compared to placebo in patients in first remission after intensive chemotherapy (IC) who were not eligible for allogeneic hematopoietic cell transplant (alloHCT) (Wei et al. NEJM. 2020). Herein, we examined the characteristics and real-world clinical practice/outcomes of patients who had received Oral-AZA.

Methods: This was a retrospective study of AML patients who were treated at the Moffitt Cancer Center between 9/2020 and 6/2024 who had received Oral-AZA after achieving CR/CRi. Patients who started Oral-AZA after alloHCT were excluded. Descriptive statistics were performed. Kaplan-Meier analysis with log-rank test was used to estimate RFS and OS from the time of Oral-AZA initiation.

Results: There were 65 patients (39M/25F) identified with a median age of 65 (range: 21-75) at Oral-AZA initiation. Majority of the patients were diagnosed with de novo AML (78%). According to 2022 European LeukemiaNet (ELN) classification, 30 (46.2%), 14 (21.5%), and 21 (32.3%) had favorable, intermediate, and adverse risk disease, respectively. Frequently mutated genes included NPM1 (44.6%), FLT-ITD/TKD (27.7%), NRAS (24.6%), and IDH1/2 (13.8%). Prior to Oral-AZA initiation, 72.3% had 1 line of therapy (range: 1-3). Over 90% of patients received cytarabine-based induction. A total of 90.8% (59/65) received consolidation with a median of 2 cycles. The median time to Oral-AZA initiation from induction or consolidation chemotherapy was 63 days.

Median duration of Oral-AZA was 4 cycles and 16.9% remained on the drug for ≥12 months. Notably, 17 out of 65 patients (26.1%) in our cohort received alloHCT after Oral-AZA maintenance (median 3 cycles). Median follow-up was 15.5 months and OS from Oral-AZA initiation was not reached with OS rates of 93.3% (95% CI: 83.1-97.4) and 84.8% (95% CI: 71.6-92.2) at 6 and 12 months, respectively. Median RFS was 17.9 months with 6- and 12-month RFS rates of 79.4% (95% CI: 66.5-87.7) and 63.6% (95% CI: 48.6-75.3), respectively.

When patients who ended up receiving alloHCT after Oral-AZA were excluded (n=48), median OS was also not reached and OS rate at 12 months was 82.3% (95% CI: 66.1-91.2 %). In the subset of patients who had NPM1 at diagnosis (n=29), percent survival at 12 months was 95.2% (95% CI: 70.7-99.3 %). The median RFS in NPM1 positive patients who did not receive alloHCT was 26.9 months with RFS rates of 80.0% (95% CI: 49.98-93.07) and 53.3% (95% CI: 23.39 - 76.19) at 6 and 12 months respectively. There were 17 patients age < 55 and their survival was 100% at 12 months and 85.7% at 24 months.

Measurable residual disease (MRD) by flow cytometry was available for 22/65 (33.8%) patients prior to Oral-AZA initiation, and 11/22 (50%) of these patients had subsequent flow MRD assessments. All patients remained MRD negative by flow while on Oral-AZA. Four of the 22 patients did eventually relapse.

Conclusions: Our results affirm the survival benefits observed with the use of Oral-AZA maintenance in the QUAZAR AML-001 study in the real-world setting. The outcome of those who harbor NPM1 is especially favorable. In the subset of patients who ended up receiving alloHCT, maintenance therapy with Oral-AZA was used as bridging therapy for relapse prevention prior to transplant. The benefit of this strategy will need to be confirmed with larger dataset and be validated prospectively.

Chan:Abbvie: Honoraria, Research Funding; Syndax: Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding; Novartis: Honoraria; Aptitude Health: Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Tobon:Eli Lilly: Consultancy, Honoraria, Other: Consultant/Advisory Board; Abbvie: Consultancy, Honoraria, Other: Consultant/Advisory Board; Bristol Myers Squibb: Consultancy, Honoraria, Other: Completed non-CE panel discussion. Lancet:Prelude Therapeutics: Consultancy, Other: Bristol Myers Squibb; Bristol Myers Squibb: Consultancy, Other: Consultant/Advisory Board; Tradewell Therapeutics: Consultancy, Other: Consultant/Advisory Board. Sallman:Abbvie: Consultancy; Agios: Consultancy; Axiom: Consultancy; Gilead: Consultancy; Celyad: Consultancy; Froghorn: Consultancy; Incyte: Consultancy; Intellisphere, LLC: Consultancy; Johnson & Johnson: Consultancy; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; NextTech: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AvenCell: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Dark Blue Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Membership on an entity's Board of Directors or advisory committees; NKARTA: Membership on an entity's Board of Directors or advisory committees; Orbital Therapeutics: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Apera: Research Funding; Jazz: Research Funding. Komrokji:CTI biopharma: Membership on an entity's Board of Directors or advisory committees; Servio: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Keros: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servio: Honoraria; Taiho: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Kuykendall:Novartis: Research Funding; Protagonist Therapeutics: Honoraria, Research Funding; PharmaEssentia: Honoraria; Incyte: Honoraria.

Off-Label use of Oral Azacitidine for maintenance in AML after first remission in HSCT eligible patients. This was used as a bridge to transplant for relapse prevention.