BACKGROUND: Oral azacitidine (Oral-AZA) was approved in Canada in January 2021 as maintenance therapy for patients (pts) with acute myeloid leukemia (AML) in remission after induction therapy who are not eligible for hematopoietic stem cell transplantation (HSCT). Real-world evidence (RWE) on Oral-AZA use and its effectiveness in the AML population is needed to help contextualize available trial data and inform clinical practice.
AIMS: To describe pt characteristics, treatment patterns, survival, and safety outcomes of pts with AML who received Oral AZA maintenance therapy in Canada.
METHODS: We conducted a retrospective, observational medical record review of pts with AML in remission after induction therapy and treated with Oral-AZA in Canada. We excluded pts who had participated in a clinical trial or had received prior HSCT. Pts were required to have started Oral AZA treatment from March 2021 to July 2023. The start date of Oral-AZA defined the study index date. Data were collected from August 2023 through November 2023. Time-to-event outcomes were estimated using the Kaplan-Meier methods.
RESULTS: Data from 119 pts with AML who initiated Oral-AZA between 1 April 2021 and 12 July 2023 were analyzed. Most pts were white (73.1%), male (61.3%), and were diagnosed with de novo AML (85.7%). The median age at Oral-AZA initiation was 62.5 years with 21.0% of pts aged <55. The genetic risk status based on the 2017/2022 ELN classification (most recent available) was favorable for 47 (39.5%), intermediate for 47 (39.5%), and adverse for 23 (19.3%) pts. The most frequently reported gene mutations were NPM1 in 22 (18.5%) pts, CEBPA in 13 (10.9%), IDH2 in 10 (8.4%), FLT3-TKD in 9 (7.6%), FLT3-ITD in 8 (6.7%), and IDH1 and ASXL1 in 7 (5.9%) pts each. The median baseline Hematopoietic Cell Transplantation-Comorbidity Index score was 1.0, and 70.2% of pts (66/94) had an ECOG PS of 0-1. Nearly all patients (99.2%) received cytarabine-based induction regimens, including standard 7+3 and CPX-351, among others. A total of 55.5% (66/119) pts received consolidation therapy with a median of 2 cycles, and 33.0% (22/66) received ≥3 cycles. After a median follow-up of 9.4 months, 81 pts (68.1%) were still receiving Oral-AZA at last follow-up/visit. The duration of Oral-AZA treatment was 1-3 months (mos) for 27.7% of pts, 4-6 mos for 21.8%, 7-11 mos for 20.2%, and ≥12 mos for 30.3%. Most pts (79.0%) started Oral AZA at 300 mg for 14 days/cycle; 55.5% received this dose at treatment discontinuation or last follow-up/visit. In total, 67.2% of pts experienced ≥1 adverse event (AE) during Oral-AZA treatment with nausea (46.2%), fatigue (34.5%), and vomiting (19.3%) being the most common AEs. Concomitant antiemetic treatment was received by 78.2% of pts. Six- and 12-mo overall survival rates from Oral-AZA initiation were 89.0% (standard error [SE]:3.1) and 74.5% (SE:5.0), respectively. Six- and 12-mo real-world, relapse-free survival rates after Oral-AZA initiation were 82.5% (SE:3.8) and 66.9% (SE:5.3), respectively.
SUMMARY/CONCLUSION: Real-world survival outcomes of pts with AML in remission treated with Oral AZA were consistent with those reported in the QUAZAR trial. More than half of the pts were still receiving treatment at the time of data abstraction and about one-third received ≥12 mos of therapy, indicating that long-term Oral-AZA treatment is feasible in clinical practice. Oral-AZA had a manageable safety profile with reported AEs consistent with Oral-AZA clinical trials. Our results provide RWE supporting the use of Oral AZA maintenance therapy in clinical practice for pts with AML ineligible for HSCT.
