PB2094 A SINGLE CENTRE EXPERIENCE WITH AZACITIDINE FOR MDS, AML AND CMML IN RELATION TO CYTOGENETIC RISK AND PERFORMANCE STATUS
Bibliographic record
Abstract
Background: Azacitidine is a hypomethylating agent which is used in the treatment of myelodysplastic syndromes (MDS), acute myeloid leukaemia (AML) and chronic myelomonocytic leukaemia (CMML). In the AZA‐001 trial, azacitidine altered the natural history of patients with higher‐risk MDS (Fenaux et al., Lancet 2009) by significantly improving overall survival (OS) compared to conventional care regimens (24.5 months vs 15.0 months) and in particular improved OS in the poor risk cytogenetics group (17.4 months vs 6 months) which led to its NICE approval in 2011. Aims: We report a single centre experience over 4 years of using azacitidine in the licensed NICE indications and compared results to the published data. Methods We retrospectively reviewed patients with MDS, AML and CMML who received azacitidine at Ipswich Hospital NHS Trust between November 2014 and November 2018. Data was collected on demographics, disease characteristics, treatment, blood and platelet transfusion response, disease progression and cause of death Results: Thirty‐nine patients met the NICE criteria for treatment and were included in the analysis, irrespective of the number of cycles received. Median age was 72.2 years. Male: Female ratio was 2:1. Median number of cycles was 9 (range from 1‐43). 51% of patients had a diagnosis of MDS, 31% AML and 18% CMML. 25.6% had poor risk cytogenetics as per the IPSS criteria. Median percentage of blasts on bone marrow aspirate was 15.7%. Causes of death were either disease progression or sepsis with only one death unrelated to the underlying condition (lung cancer). Median Kaplan‐Meier OS for all groups from the start of treatment with azacitidine was 18 months, with MDS patients OS of 22 months compared to 18 months for AML and 13 months for CMML (p = 0.22). There was a significant difference noted in the group who had poor risk (IPSS) cytogenetics versus other cytogenetic risks, with a median OS of 8 months and 20 months respectively (p = 0.002). A significant difference was also seen in the median OS based on performance status (PS), with an OS of 7 months, 20 months and not yet reached for PS 2, 1 and 0 respectively (p = 0.005). Summary/Conclusion: In the AZA‐001 trial median OS on azacitidine was 24 months vs. 18 months seen in our cohort. The AZA‐001 trial also showed improved OS for poor risk cytogenetics at 17.4 months vs. only 8 months seen in our experience. Although our data does support an overall improvement in median OS for all groups, our data showed less impressive results, with a 6 months less survival advantage in all groups and 9 months less OS in the poor cytogenetic group as compared to the trial data. As previously shown, we observed that the most significant factors in predicting OS were cytogenetic risks and PS. Interestingly, a large real world registry collection in Canada of 1101 patients on azacitidine over 6 years only showed a median OS of 12 months for all groups which further highlights the difference we often see between real world patients and trial data.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".