Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C

Abstract

In the phase III AZA-001 trial, low-dose cytarabine (LDara-C), the most widely used low-dose chemotherapy in patients with higher-risk myelodysplastic syndrome (MDS) who are ineligible for intensive treatment, was found to be associated with poorer survival compared with azacitidine. This analysis further compared the efficacy and the toxicity of these two drug regimens. Before randomization, investigators preselected patients to receive a conventional care regimen, one of which was LDara-C. Of 94 patients preselected to LDara-C, 45 were randomized to azacitidine and 49 to LDara-C. Azacitidine patients had significantly more and longer haematological responses and increased red blood cell transfusion independence. Azacitidine prolonged overall survival versus LDara-C in patients with poor cytogenetic risk, presence of -7/del(7q), and French-American-British subtypes refractory anaemia with excess blasts (RAEB) and RAEB in transformation. When analyzed per patient year of drug exposure, azacitidine treatment was associated with fewer grade 3-4 cytopenias and shorter hospitalisation time than LDara-C in these higher-risk MDS patients.

Fig 1

Unadjusted Kaplan–Meier estimated overall survival: azacitidine (AZA) versus low dose cytarabine (LDara-C).

Fig 2

Hazard ratio and 95% CI for overall survival by FAB subtype and cytogenetic risk (the horizontal axis has a logarithmic scale). FAB, French-American-British; RAEB, refractory anaemia with excess blasts; RAEB-tm, RAEB in transformation; ITT, intention to treat; AZA, azacitidine.

Fig 3

Mean (±SE) changes from baseline for haemoglobin (A), platelets (B) and absolute neutrophil count (C). *‘Last observation carried forward’ methodology used for both azacitidine and LDara-C groups.