Azacitidine Improves Outcome in Patients with MDS and AML with High Risk Cytogenetics - a Single Center Experience

Azacitidine is a novel hypomethylating agent shown to improve leukaemia free survival and overall survival in comparison with other modalities of treatment in MDS and AML patients. There is proven reduction in transfusion requirements by improvement in haematological parameters with continuous azacitidine use. However azacitidine benefit in high risk cytogenetics group is unclear. Recent retrospective study from GESMD and GFM registries showed that Azacitidine improves outcome in higher‐risk MDS patients with chromosome 7 abnormalities. Here we report our experience in high risk cytogenetics group including complex karyotype.

Methodology:-

We retrospectively reviewed patients with MDS and AML who received Azacitidine at the Heart of England NHS Foundation Trust from April 2012- January 2018. Patient's demographic data, disease characteristics, treatment, outcome and follow up data were obtained and all patients were included irrespective of the number of the cycles.

Results

57 patients were included in the analysis. Median age of treatment was 73.9 years. Median number of cycles was 6 (range from 1 to 43). There were 68% of MDS patients, 22.8% of AML and 8.8% of CMML2 patients in the cohort .Varying degree of performance stage was noted including ECOG 0,1 and 2 at 40.4%,43.9% and 7.7% respectively. 9 patients had monosomy 7 and 11 patients had complex karyotype (3/>3). 42.1% had high risk cytogenetics.

At presentation, median Hb was 9g/dl, Neutrophil count was 0.7x109/l and platelet count was 41x109/l. Median bone marrow blast percentage was10% and median RIPSS score was 6.5. Causes of death were mainly disease progression and sepsis. 42.2% died due to disease progression and 35.1% died due to sepsis.

Overall survival was not affected by age, Bone marrow median blast percentage and median neutrophil count, however, survival was affected by presenting peripheral blast percentage, cytogenetic risk group and was statistically significant (P<0.05)

Overall, median progression free survival (PFS) was 19monts while median overall survival (OS) was 12 months. There was no statistically significant PFS or OS difference for patients who had varying performance stage.

High risk cytogenetics group:

Among high risk cytogenetics group, 21% Patients had red cell transfusion independence at 6 months, 28% had an improvement in the neutrophil count to >1x10^9/L at 6 months. 25% patients had doubling of platelet count at 3 months leading to platelet independence and 17.8% maintained platelet transfusion independence. A significant difference was noted in the group of who had high risk cytogenetic versus other cytogenetic risks with PFS of 15 and 29 months respectively, OS of 8 months and 15 months respectively. with high risk cytogenetics still had a PFS advantage with treatment.

Conclusion

Azacidine therapy has benefited for the patients who had advanced age AML CMML and MDS who has non high risk cytogenetic based on IPSS-R risk categorization. However, the group of patients with high risk cytogenetic considered historically very poor survival had considerable PFS and OS benefitting treatment rather than best supportive care.

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