Efficacy and safety of azacitidine in the treatment of elderly patients with higher-risk myelodysplastic syndromes.
Bibliographic record
Abstract
e18578 Background: Hypomethylating agent Azacitidine (AZA) is standard of care for high-risk myelodysplastic syndromes (MDS). There is limited real-life data, however, characterizing the efficacy and safety profile of AZA in elderly patients. Methods: A retrospective chart review of high-risk MDS patients at our institution who received front-line AZA therapy. Patients who proceeded with stem cell transplant were excluded. Patients were stratified by age: ≥75 years (elderly) vs <75 years (younger) and patterns of administration, safety, and efficacy of AZA in patients were compared. Results: Among a total of 105 patients, 56 were elderly (median age 79), including 27 patients >80 years, 49 were younger (median age 69). ECOG 3 had 8.9% of older & 12.2% of younger patients. Median R-IPSS score was 6.5 in younger vs 5.8 in elderly groups. Median number of comorbidities was 5 vs 6 in younger and elderly groups. 98% of elderly and 90% of younger patients received the full dose of AZA (75mg/m2). Median number of AZA cycles was 8 [range 1-107] in elderly vs 6 [1-96] in younger cohorts. Treatment delays had 35.7% of elderly vs 30.6% of younger patients, most commonly due to infection complications. Neutropenia, thrombocytopenia and anemia rates were 29.3%, 29.2%, and 26.8% in younger vs 43.6%, 25.2%, and 34.5% in older patients. Overall response rate was 92.8% in younger and 96.4% of elder patients, including complete remission in 53.7% and 58.3%, respectively. Relapse disease occurred in 48.8% of younger and 40.0% of elder patients. Transformation to AML was found in 9.8% of younger and 19.2% of elderly patients. Median OS was 17.3 months in the younger subgroup vs 15.7 in the elder group and 11.9 months in patients over 80 years. Rates of death were: 53.1% in younger vs 46.4% in the elderly. Causes of death were similar, including disease progression, sepsis, febrile neutropenia, pneumonia. Conclusions: AZA monotherapy is well-tolerated and effective in higher-risk MDS, even in very elderly patients (>80 years). Compared to clinical trial, patients in the real-world setting have shorter survival, higher ECOG status, and more comorbidities, potentially contributing to inferior outcomes. Clinical and hematological responses. Efficacy parameter/Age cohort, years (N) <75 (49) ≥75 (56) p value Hematological Response (median [min-max]) Baseline Hemoglobin (g/L) 77 [46-100] 80 [56-140] 0.014 Best Hemoglobin achieved on AZA (g/L) 103 [74-152] 108 [70-155] NS Baseline ANC (x10 9 /L) 0.7 [0-27] 0.89 [0.02-58] NS Best ANC achieved on AZA (x10 9 /L) 1.4 [0.02-12.3] 2.2 [0.04-9.6] 0.047 Baseline platelet count (x10 9 /L) 49 [2-600] 57 [16-558] 0.029 Best achieved on AZA (x10 9 /L) 128 [21-474] 155 [10-767] NS Transformation to AML N, (%) 4 (9.8) 10 (18.2) NS Reached transfusion independence, N (%) 30 (61.0) 38 (67.2) NS Response rate, N (%) ORR 46 (92.8) 54 (96.4) NS Complete Response 26 (53.7) 33 (58.2) NS Partial Response 11 (22.0) 11 (20.0) NS Stable Disease 8 (17.1) 10 (18.2) NS Mean Leukemia Free Survival (years) 1.13 1.05 NS Mean Overall Survival (years) 1.14 1.05 NS
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".