Effects of Azacitidine (AZA) Vs Conventional Care Regimens (CCR) in Elderly (≥75 years) Patients (Pts) with Myelodysplastic Syndromes (MDS) from the AZA-001 Survival Trial

Background. A recent phase III trial (AZA-001) showed AZA is the first treatment to significantly extend overall survival (OS) in higher-risk MDS patients (pts) (

Methods. Higher-risk MDS (FAB: RAEB, RAEB-T, CMML and IPSS: Int-2 or High) pts were enrolled. All pts were pre-selected by site investigators – based on age, performance status, and comorbidities – to receive 1 of 3 CCR: best supportive care only (BSC); lowdose ara-C (LDAC), or intensive chemotherapy (IC). Pts were then randomized to AZA (75 mg/m²/d SC × 7d q 28d), or to CCR. Those randomized to AZA received AZA; those randomized to CCR received their pre-selected treatment. Randomization was stratified based on FAB subtype (RAEB and RAEB-T) and IPSS (Int-2 or High). Erythropoiesis stimulating agents were disallowed. OS was assessed using Kaplan-Meier (KM) methods and HI and TI were assessed per IWG 2000. To adjust for baseline imbalances, a Cox proportional hazards model was used, with ECOG status, LDH, number of RBC transfusions, Hgb, and presence or absence of -7/del(7q) at baseline as variables in the final model. Adverse events (AEs) were evaluated using NCI-CTC v. 2.0.

Results. Of all enrolled pts (N=358, median age 69 yrs), 87 pts (24%) were ≥75 yrs of age (AZA n=38, CCR n=49 [BSC, n=33; LDAC, n=14; IC, n=2]). The majority of pts randomized to CCR received BSC only, suggesting clinicians are generally reticent to use active treatment in this population. Similar to the overall AZA-001 results, treatment with AZA was associated with prolonged survival in pts ≥75 yrs of age, with KM median OS in the AZA group not reached at 17.7 months of follow-up, vs KM median OS for CCR at 10.8 months (HR: 0.48 [95%CI: 0.26, 0.89]; p=0.0193). In these pts, OS rates at 2 years were significantly higher in the AZA group vs CCR: 55% vs 15% (p=0.0003). Two-fold more RBC transfusion-dependent pts at baseline in the AZA group achieved TI vs CCR: 10/23 (44%) vs 7/32 (22%), p=0.1386, respectively. Similarly, more pts in the AZA group achieved HI (major + minor) vs CCR: 58% vs 39%, (p=0.0875), respectively. As previously reported, AZA was generally well tolerated. Anemia, neutropenia, and thrombocytopenia were seen in 42%, 66%, and 71% of pts in the AZA group, respectively, vs 47%, 26%, and 40% in the CCR group, who were predominately receiving BSC only. Infections were reported by 79% and 60% of AZA and CCR pts, respectively. Discontinuations due to an AE occurred in 13% of AZA and 8% of CCR pts ≥75 yrs of age.

Conclusion. Data from this subgroup analysis indicate pts ≥75 yrs of age with higher-risk MDS receiving active treatment with AZA experience significantly prolonged 2-year OS and reduced risk of death. AZA is generally well tolerated in this elderly patient population.