Advanced Age Does Not Compromise Azacitidine Outcomes in Higher-Risk Myelodysplastic Syndromes

Clinical Summary:

• Design/Population: This retrospective, single-center study evaluated frontline azacitidine in elderly (≥75 years) versus younger (<75 years) patients with higher-risk myelodysplastic syndromes, including a subgroup of patients >80 years. 
• Key Outcomes: Disease control, overall survival, and transfusion independence were comparable between age groups despite advanced age and comorbidities. Azacitidine was generally well tolerated, with similar rates of treatment delays, adverse events and mortality across age groups.
• Clinical Relevance: These real-world findings support azacitidine as an effective and well-tolerated first-line treatment for appropriately selected elderly patients with higher-risk myelodysplastic syndromes, suggesting that advanced age alone should not preclude its use. 

Results from a retrospective, real-world study demonstrated that azacitidine produced comparable efficacy and tolerability in elderly and younger patients with higher-risk myelodysplastic syndromes, supporting its continued use as first-line therapy regardless of age. 

“Azacitidine is the standard of care for patients with higher-risk myelodysplastic syndromes… [yet] there is limited real-life data characterizing its efficacy and safety profile in elderly patients,” stated Nupur Krishnan, MD, McMaster University, Hamilton, Ontario, Canada, and coauthors. 

In this single-center cohort study, researchers collected data from 96 patients with higher-risk myelodysplastic syndromes who received at least 1 dose of azacitidine between June 2010 and June 2024. Patients were stratified by age into younger (<75 years; n = 41) and elderly (≥75 years; n = 55) cohorts, including a subgroup of 27 patients >80 years. 

The primary end point was overall survival (OS). Key secondary end points included response according to the 2006 International Working Group criteria, leukemia-free survival, transfusion independence, and safety.

At analysis, 98% of patients in the elderly cohort received the full recommended azacitidine dose (75 mg/m²) compared with 90% of patients in the younger cohort. Median treatment duration was similar (8 cycles vs 7.75 cycles). Treatment delays were reported in 36.4% of patients and 29.3% of patients, respectively (P = .076). 

Median OS was 15.7 months in the elderly cohort and 17.3 months in the younger cohort (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.59 to 1.41; P = .771). Among patients >80 years, median OS was 11.9 months, with no significant difference compared with the remainder of the elderly cohort (P = .381). Leukemia-free survival was 14.1 months and 12.1 months, respectively (HR, 0.91; 95% CI, 0.59 to 1.39; P = .739). 

Disease control rates were similar between younger and elderly patients (92.8% vs 96.4%; P = .154), with complete remission achieved in 53.7% and 58.2% of patients, respectively. Red blood cell transfusion independence occurred in 61% of younger patients and 67.3% of elderly patients (P = .156). Relapse occurred in 48.8% and 40% of patients, respectively, whereas transformation to acute myeloid leukemia was more common among elderly patients (18.2% vs 9.8%; P < .016).

The most common hematologic adverse events were neutropenia, thrombocytopenia, and anemia. Disease progression was the leading cause of death in both cohorts and occurred more frequently in the elderly cohort, although this difference was not statistically significant (36.4% vs 26.8%; P = .078). Deaths due to febrile neutropenia occurred at similar rates (12.2% vs 12.7%), whereas bleeding-related mortality was more common among younger patients (7.3% vs 3.6%; P = .041).

“Moving forward, multicenter real-world studies would be valuable to further strengthen the robustness and generalizability of these findings,” concluded Dr Krishnan et al. “In addition, future research should aim to identify molecular biomarkers and clinical predictors of response or prognosis.”

Source:

Krishnan N, Yanni D, Kogan L, et al. Azacitidine is well-tolerated and is associated with high response rate in elderly patients with higher-risk myelodysplastic syndromes: A single center observational study. Cancers (Basel). Published online: June 30, 2026. doi: 10.3390/cancers18132131