Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN
Bibliographic record
Abstract
ABSTRACT: Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and/or mutated TP53, and 17% had complex karyotype (CK; ≥3 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and/or mutated TP53, or CK had significantly improved PFS with acalabrutinib ± obinutuzumab vs chlorambucil-obinutuzumab (P < .0001, P ≤ .0009, and P < .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after >4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".