P643: CUMULATIVE REVIEW OF HEART FAILURE WITH ACALABRUTINIB IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA USING DATA FROM CLINICAL TRIALS AND POST-MARKETING EXPERIENCE
Bibliographic record
Abstract
Background: Bruton tyrosine kinase inhibitors (BTKis) have revolutionized treatment for several B-cell malignancies. However, the first-generation BTKi ibrutinib has been linked with cardiac toxicities including atrial fibrillation, ventricular tachyarrhythmias, hypertension, and heart failure (HF). The predominantly elderly population with chronic lymphocytic leukemia (CLL) is expected to be at increased risk of cardiovascular disease, including HF. Aims: To review the acalabrutinib safety profile with respect to HF based on phase 3 randomized clinical trial data and the global acalabrutinib safety database. Methods: Safety data were obtained from 3 phase 3 CLL trials (ELEVATE-RR, ELEVATE-TN, ASCEND) and from the global acalabrutinib safety database, which includes all clinical trial and post-marketing data for acalabrutinib. In the individual phase 3 clinical trials for the acalabrutinib and active comparator arms, exposure-adjusted (exp-adj) incidence rates (events/100 person-months) were reported for “cardiac failure” (CF) using the broad Standardized MedDRA Query (SMQ; comprising CF-specific and CF-related terms) and the MedDRA preferred terms (PT). Exp-adj incidence rates of CF also were reported based on a cumulative comprehensive search of the global acalabrutinib safety database. Results: In the 3 clinical trials, 598 patients were treated with acalabrutinib monotherapy, 178 with acalabrutinib + obinutuzumab, and 586 with comparator anti-neoplastic agents. In each of the 3 clinical trials, the overall exp-adj incidence rates of any-grade and grade ≥3 CF (SMQ) were numerically lower in the acalabrutinib arms vs comparator arms; the most common PTs were generally numerically lower in the acalabrutinib arms (Table). The exp-adj incidence rate of any-grade CF (PT) in the acalabrutinib arms across the 3 trials ranged from 0.03 to 0.06 (Table); the corresponding exp-adj incidence rate of any-grade CF from the global acalabrutinib safety database (post-marketing sources only) was 0.008. In the global acalabrutinib safety database, a total of 779 CF (SMQ) events were captured (727 from post-marketing sources), of which the most commonly reported CF terms were peripheral swelling (n=406), edema peripheral (n=99), edema (n=56), and pulmonary edema (n=47). Summary/Conclusion: Cumulatively, overall exp-adj incidence estimates for CF events from 3 clinical trials in CLL were not higher with acalabrutinib monotherapy than with other antineoplastic agents, irrespective of severity. Data from the clinical trial and global safety databases do not suggest that acalabrutinib is associated with a substantially higher risk of CF.Keywords: Clinical trial, Chronic lymphocytic leukemia, Safety
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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 | 0.013 | 0.031 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.011 | 0.013 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".