Pooled safety analysis of omacetaxine mepesuccinate in patients with chronic myeloid leukemia (CML) resistant to tyrosine-kinase inhibitors (TKIs).
Bibliographic record
Abstract
6604 Background: Subcutaneous omacetaxine mepesuccinate (“omacetaxine”) is a reversible, transient inhibitor of protein elongation that does not depend on BCR-ABL signaling. It showed significant clinical activity in two phase 2, open-label, multicenter studies of patients with CML who were resistant/intolerant to prior TKI therapy. However, omacetaxine tolerability data across the 3 phases of CML are limited. Methods: Safety data were pooled from all patients in the 2 studies plus a small pilot study. Omacetaxine 1.25 mg/m2 was given subcutaneously twice daily: ≤14 successive days per 28-day cycle for induction, ≤7 days/cycle as maintenance. Days of dosing could be adjusted and recombinant growth factors given, as clinically indicated. Results: Of 207 pooled patients (median age, 57 years), 108 were in chronic (CP), 55 in accelerated (AP), and 44 in blast phase (BP). Median treatment was 4 cycles (range, 1–41). On study, 80% of patients had ≥1 hematologic adverse event (AE), 60% had a serious AE (SAE), 30% had a hematologic SAE, 34% had an SAE that resulted in hospitalization, and 15% discontinued treatment due to an SAE (most commonly disease progression). There were 49 (24%) deaths (15 CP, 11 AP, and 23 BP). Of the 8 that were treatment related (5 CP, 2 AP, 1 BP), the most common cause was sepsis (3 patients). The most common AEs were thrombocytopenia (60%), anemia (51%), diarrhea (40%), neutropenia (37%), and nausea (30%). Injection site reactions (eg, injection site pain, erythema) occurred in 32%, with the majority being low grade. Infections (eg, pneumonia, bronchitis) occurred in 51%. Treatment-related grade 3/4 hematologic AEs included thrombocytopenia (52%), neutropenia (31%), anemia (30%), leukopenia (12%), and febrile neutropenia (11%). The most common treatment-related grade 3/4 nonhematologic AE was fatigue (4.3%). Overall, there were 34 (16%) grade 3/4 infections (12 CP, 11 AP, 11 BP). Conclusions: In the largest safety analysis to date, subcutaneous omacetaxine 1.25 mg/m2 showed an acceptable safety profile in all phases of CML. AEs were primarily hematologic, and grade 3/4 nonhematologic AEs were not common. Support: Teva Pharmaceutical Industries Ltd.
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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 | 0.009 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.005 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".