Contributions
Type: Publication Only
Background
The hypo-methylating agent, 5-azacitidine, is used to treat chronic myelomonocytic leukaemia (CMML), intermediate and high-risk myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) with 20-30% blasts in patients unsuitable for high intensity treatment. Our centre is one of the largest users of azacitidine in the South East of England, reflecting the predominantly elderly population served.
Aims
To evaluate overall survival (OS) of patients treated with 5-azacitidine at our centre. Comparison of OS for MDS and AML groups and according to cytogenetic prognostication. Also to compare local prescribing practice with 2011 guidelines published by the National Institute for Clinical Excellence (NICE).
Methods
A retrospective analysis of medical records for all patients treated with four weekly cycles of 5-azacitidine (75mg/m2) for 7 days. Patients were grouped according to diagnosis (MDS, CMML or AML) and cytogenetic classification as per the 5-group MDS Revised International Prognostic Scoring System (IPSS-R).
Results
Forty-two patients (n=19 AML, n=22 MDS, n=1 CMML) were identified from a 40 month observation period. Mean age was 71 (range 43-84). The median time from diagnosis to treatment was 17 days. The mean number of cycles received was 6 (range 1-23). Eighteen patients were diagnosed and received 5-azacitidine after treatment for a previous haematological malignancy: relapsed AML (n=7); transformed MDS (n=4); myeloproliferative disorder (n=3); MDS following AML treatment (n=2); chronic lymphocytic leukaemia (n=1); myeloma (n=1).
Kaplan-Meier analysis revealed an OS of 9.77 months for all 42 patients (95% CI 6.55-12.98). OS for MDS patients was 12.11 (CI 7.69-16.5). OS for MDS subgroups according to cytogenetic prognostic groups ‘good’, ‘intermediate’, ‘very poor’ and ‘unknown’ were 15.7 (n= 9, CI 7.7-23.7), 8.25 (n=4, CI 6.44-10.05), 3 (n=4, CI 0.23-5.77), and 10.6 (n=5, CI 2.48-18.72), months respectively. The ‘good’ cytogenetic group had significantly longer OS compared to ‘bad’ cytogenetics, P<0.001. OS for AML patients was 6.34 (CI 2.02-10.7) significantly worse when compared to all MDS patients, P=0.001. Twenty-nine patients (69%) met NICE approval criteria. Treatment outside the criteria was due to either no alternative available (9), instruction from regional transplant centre (3) or as part of a trial (1). Treatment within NICE recommendations showed significantly improved survival (P=0.001) with a mean of 13.27 months (CI 9.32-17.23) compared to 2.73 (CI 1.84-3.67).
Summary
Treatment with 5-azacitidine for AML and MDS gave OS of 12.11 and 6.34 months respectively in our elderly population with limited alternative therapeutic options. Favourable prognostic cytogenetics and treatment within national guidelines led to superior survival in this sample.
Keyword(s): Acute myeloid leukemia, Hypomethylation, Myelodysplasia, Survival
Type: Publication Only
Background
The hypo-methylating agent, 5-azacitidine, is used to treat chronic myelomonocytic leukaemia (CMML), intermediate and high-risk myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) with 20-30% blasts in patients unsuitable for high intensity treatment. Our centre is one of the largest users of azacitidine in the South East of England, reflecting the predominantly elderly population served.
Aims
To evaluate overall survival (OS) of patients treated with 5-azacitidine at our centre. Comparison of OS for MDS and AML groups and according to cytogenetic prognostication. Also to compare local prescribing practice with 2011 guidelines published by the National Institute for Clinical Excellence (NICE).
Methods
A retrospective analysis of medical records for all patients treated with four weekly cycles of 5-azacitidine (75mg/m2) for 7 days. Patients were grouped according to diagnosis (MDS, CMML or AML) and cytogenetic classification as per the 5-group MDS Revised International Prognostic Scoring System (IPSS-R).
Results
Forty-two patients (n=19 AML, n=22 MDS, n=1 CMML) were identified from a 40 month observation period. Mean age was 71 (range 43-84). The median time from diagnosis to treatment was 17 days. The mean number of cycles received was 6 (range 1-23). Eighteen patients were diagnosed and received 5-azacitidine after treatment for a previous haematological malignancy: relapsed AML (n=7); transformed MDS (n=4); myeloproliferative disorder (n=3); MDS following AML treatment (n=2); chronic lymphocytic leukaemia (n=1); myeloma (n=1).
Kaplan-Meier analysis revealed an OS of 9.77 months for all 42 patients (95% CI 6.55-12.98). OS for MDS patients was 12.11 (CI 7.69-16.5). OS for MDS subgroups according to cytogenetic prognostic groups ‘good’, ‘intermediate’, ‘very poor’ and ‘unknown’ were 15.7 (n= 9, CI 7.7-23.7), 8.25 (n=4, CI 6.44-10.05), 3 (n=4, CI 0.23-5.77), and 10.6 (n=5, CI 2.48-18.72), months respectively. The ‘good’ cytogenetic group had significantly longer OS compared to ‘bad’ cytogenetics, P<0.001. OS for AML patients was 6.34 (CI 2.02-10.7) significantly worse when compared to all MDS patients, P=0.001. Twenty-nine patients (69%) met NICE approval criteria. Treatment outside the criteria was due to either no alternative available (9), instruction from regional transplant centre (3) or as part of a trial (1). Treatment within NICE recommendations showed significantly improved survival (P=0.001) with a mean of 13.27 months (CI 9.32-17.23) compared to 2.73 (CI 1.84-3.67).
Summary
Treatment with 5-azacitidine for AML and MDS gave OS of 12.11 and 6.34 months respectively in our elderly population with limited alternative therapeutic options. Favourable prognostic cytogenetics and treatment within national guidelines led to superior survival in this sample.
Keyword(s): Acute myeloid leukemia, Hypomethylation, Myelodysplasia, Survival