Contributions
Type: Publication Only
Background
Azacitidine is a hypomethylating agent with demonstrated efficacy in high risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The trials that have led to its approval for these indications excluded patients with leucocytosis and most observational studies suggest that it is less efficacious in patients with proliferative disease.
Aims
We present a single-centre retrospective analysis of the efficacy of azacitidine in 18 with MDS, CMML and AML with proliferative features and compare these with a similar cohort of patients with non-proliferative disease.
Methods
Data was collected retrospectively from clinical files following ethical committee approval
Results
The cohort with proliferative disease, defined by a leukocytosis >13x109/L, had a median age at diagnosis of 67 years; 55% were men. WHO 2008 diagnosis was MDS in 2 patients, AML in 8 patients and CMML in 8 patients. At diagnosis, the median hemoglobin was 8.9 g/dL (range 6.5-13.0), median WBC was 34.7x109/L (range 12.7-95.0) and median platelet count 89x109/L (range 12-695). Bone marrow blast percentage was >10% in 72% of patients; median 19% (range 1.2-98) Karyotypes were normal in 44%, intermediate risk in 27% and poor risk in 29%.
Azacitidine was used as single agent as first line therapy with no prior cytoreduction in all patients. Patients started treatment a median of 2.3 months following diagnosis. Marrow response was assessed after the 6th cycle. Treatment was continued until progression in all cases. A median number of 8 cycles were administered.
Marrow assessments were available in 16 patients. Responses were documented in 6 patients, of which 1 was complete and 5 were partial. Stable disease at time of assessment was seen in 4 patients and progression in 6. Transfusion independence was achieved in 8 of 10 patients who were previously transfusion-dependent. Four patients only received 1 cycle of treatment due to progression in 3 and pneumonia in one. Normalization of WBC was achieved in all but the former 4 patients after a median of 2.3 cycles.
All patients had died by the time of analysis, 16 due to progression, one due to pneumonia and one due to cerebral haemorrhage. Median overall survival was 15.85 months. The median survival of the comparator non-proliferative group was 11.58 months. This was not significantly different from that of the proliferative group (15.85 vs 11.58 months, respectively; log rank test: p=0.25).
Summary
These results support the use of azacitidine in patients with proliferative disease, increasing treatment options in these patients.
Keyword(s): Hypomethylation, Myelodysplasia, Proliferation
Type: Publication Only
Background
Azacitidine is a hypomethylating agent with demonstrated efficacy in high risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The trials that have led to its approval for these indications excluded patients with leucocytosis and most observational studies suggest that it is less efficacious in patients with proliferative disease.
Aims
We present a single-centre retrospective analysis of the efficacy of azacitidine in 18 with MDS, CMML and AML with proliferative features and compare these with a similar cohort of patients with non-proliferative disease.
Methods
Data was collected retrospectively from clinical files following ethical committee approval
Results
The cohort with proliferative disease, defined by a leukocytosis >13x109/L, had a median age at diagnosis of 67 years; 55% were men. WHO 2008 diagnosis was MDS in 2 patients, AML in 8 patients and CMML in 8 patients. At diagnosis, the median hemoglobin was 8.9 g/dL (range 6.5-13.0), median WBC was 34.7x109/L (range 12.7-95.0) and median platelet count 89x109/L (range 12-695). Bone marrow blast percentage was >10% in 72% of patients; median 19% (range 1.2-98) Karyotypes were normal in 44%, intermediate risk in 27% and poor risk in 29%.
Azacitidine was used as single agent as first line therapy with no prior cytoreduction in all patients. Patients started treatment a median of 2.3 months following diagnosis. Marrow response was assessed after the 6th cycle. Treatment was continued until progression in all cases. A median number of 8 cycles were administered.
Marrow assessments were available in 16 patients. Responses were documented in 6 patients, of which 1 was complete and 5 were partial. Stable disease at time of assessment was seen in 4 patients and progression in 6. Transfusion independence was achieved in 8 of 10 patients who were previously transfusion-dependent. Four patients only received 1 cycle of treatment due to progression in 3 and pneumonia in one. Normalization of WBC was achieved in all but the former 4 patients after a median of 2.3 cycles.
All patients had died by the time of analysis, 16 due to progression, one due to pneumonia and one due to cerebral haemorrhage. Median overall survival was 15.85 months. The median survival of the comparator non-proliferative group was 11.58 months. This was not significantly different from that of the proliferative group (15.85 vs 11.58 months, respectively; log rank test: p=0.25).
Summary
These results support the use of azacitidine in patients with proliferative disease, increasing treatment options in these patients.
Keyword(s): Hypomethylation, Myelodysplasia, Proliferation