Results have been announced from AML-001, a phase III study of azacitidine for injection compared to conventional care regimens (CCR) in elderly subjects with newly-diagnosed acute myeloid leukaemia (AML - >30% blasts).

The study was presented by Pr. Hervé Dombret of the Hôpital Saint-Louis in Paris, France.

In the global, multi-centre, randomised, open-label pivotal study, patients at least 65 years old with newly diagnosed or secondary AML with > 30% bone marrow blasts were pre-selected to receive one of three regimens per investigator’s choice from intensive chemotherapy (standard 7 3 regimen), low-dose Ara-C (20 mg SC twice per day for 10 days of each 28-day cycle) or best supportive care only.

Patients then randomised to receive either azacitidine (n=241) (75 mg/m2/d SC for 7 days of each 28-day cycle) or their predetermined CCR (n=247).

Median overall survival (OS), the primary endpoint of the study, was 10.4 months (95% CI 8.0-12.7 months) for patients receiving azacitidine compared to 6.5 months (5.0-8.6) for patients receiving CCR, which did not achieve statistical significance (unstratified HR=0.84 [95% CI 0.69, 1.02], p=0.0829).

Additionally, a pre-specified sensitivity analysis for OS that censored patients at the start of subsequent AML therapy was conducted.

Results of this analysis showed a longer median overall survival for patients receiving azacitidine (median 12.1 months 95% CI, range 9.2-14.2 months) compared to patients receiving CCR (median 6.9 months 95% CI range 5.1-9.6 months) (stratified HR=0.76 [95% CI 0.60, 0.96], p=0.019).

One-year survival was 47% for patients receiving azacitidine compared to 34% for patients receiving CCR.

“AML in older patients is an area of significant unmet medical need, and this study provided insight into the use of azacitidine in this population,”  said Professor Dombret.

Grade 3-4 anaemia, neutropenia, febrile neutropenia, and thrombocytopenia rates, respectively, were 16%, 26%, 28%, and 24% with azacitidine; 5%, 5%, 28%, 5% with best supportive care; 23%, 25%, 30%, 28% with low-dose Ara-C; and 14%, 33%, 31%, 21% with intensive chemotherapy.

Azacitidine for injection is not indicated for patients with acute myeloid leukaemia.

In the U.S., it is indicated for treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: refractory anaemia (RA) or refractory anaemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukaemia (CMMoL).

Source: Celgene