Real-World Treatment Patterns and Outcomes with Oral Azacitidine Maintenance Therapy in Patients with Acute Myeloid Leukemia
Authors: Krishnamurthy Pramila , Houghton Katherine , Lorenz Nicola , Williams Paula , Currie Lisa , Vigil Carlos E. , Ziba Nomthandazo , Bello Fareedat , Sieluk Jan , Strocchia Maria , Li Yeran , Kapp-Schwoerer Silke 
Published: December 2024

Introduction: In the randomized, multicenter, phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA) maintenance therapy significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with placebo for patients (pts) with acute myeloid leukemia (AML) in remission after chemotherapy who were ineligible for hematopoietic stem cell transplantation (HSCT) (Wei AH, et al. New Engl J Med 2020;383:2526-2537). Oral-AZA was approved as AML maintenance therapy by the European Medicines Agency in 2021 and has been available since June 2021 and October 2022 in Germany and England, respectively. Since the QUAZAR study was conducted (May 2013 through October 2017), the AML treatment landscape has evolved considerably with the availability of new therapies, underscoring the need for real-word data on Oral-AZA use in current medical practice.
Methods: This was a retrospective, observational study using data extracted from the medical records of pts with AML in remission after induction/consolidation therapy and treated with Oral-AZA maintenance therapy in England and Germany. Oral-AZA must have been initiated between June 17, 2021, and June 20, 2023; data were extracted April-May 2024. Pts who had participated in a clinical trial assessing investigational products or who had received HSCT before Oral-AZA were ineligible. Pt characteristics, treatment patterns, relapse, survival, and occurrence of adverse events (AEs) during Oral-AZA treatment were analyzed descriptively. Kaplan-Meier methods were used to estimate time-to-event outcomes (ie, OS and real-world RFS [rwRFS]).
Results:Data were extracted for 208 pts (England, n=108; Germany, n=100). Most pts were White (82%) and male (61%), with a median age of 67.8 years (range, 31.0-83.9) at Oral-AZA initiation; 11% of pts were &lt;55 years. The Eastern Cooperative Oncology Group performance status score was assessed for most pts (n=163; 78%) and was primarily 0 (37%) or 1 (43%). Regarding disease classification, 87% of pts were diagnosed with de novo AML. Genetic risk status assessed using the 2022 European LeukemiaNet (ELN) classification was available for 138 pts (66%) and was favorable for 65 pts (47%), intermediate for 51 pts (37%), and adverse for 22 pts (16%). The most common gene mutations at diagnosis were NPM1 (16%), RUNX1 (9%), ASXL1 (8%), and TP53 (8%). Overall, 78% of pts were treated with intensive chemotherapy induction regimens, with cytarabine + anthracycline “7+3” being the most common (55%), followed by CPX-351 (7%). Venetoclax-based regimens were given to 10% of pts. One-third (n=68; 33%) of pts received consolidation regimens, with a median of 2 cycles; 35% (n=24/68) received ≥3 cycles.
After a median follow-up of 12.8 months (mo), treatment with Oral-AZA was still ongoing for 137/208 pts (66%). The median duration of Oral-AZA treatment was 10.8 mo (range, 0.2-34.1); 6% of pts received Oral-AZA for 1-3 mo, 10% for 4-6 mo; 44% for 7-11 mo, and 39% for ≥1 year. Most pts (76%) began Oral-AZA at 300 mg for 14 days/cycle, with 69% remaining on this schedule at discontinuation/last visit. Antiemetic medication was provided to 112 pts (54%), in 96% (n=108/112) as prophylaxis. Approximately half (n=122; 59%) of pts had ≥1 AE during Oral-AZA treatment; the most common were nausea (25%) and fatigue (24%).
At 12 mo, estimated OS and rwRFS rates from Oral-AZA initiation were 88.2% (standard error [SE], 2.3) and 85.5% (SE, 2.5), respectively. Median OS and rwRFS were not reached.
Conclusions: Real-world survival outcomes of pts with AML in remission treated with Oral-AZA corroborate findings from the pivotal QUAZAR AML-001 clinical trial. Safety outcomes were consistent with the known safety profile of Oral-AZA. These findings support broad use of Oral-AZA maintenance therapy in current clinical practice for pts with AML who do not proceed to HSCT at remission.