Acalabrutinib versus rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia: ASCEND results at 4 years of follow-up.
Bibliographic record
Abstract
7538 Background: Acalabrutinib (acala) is a next-generation, highly selective, covalent Bruton tyrosine kinase (BTK) inhibitor approved for patients (pts) with chronic lymphocytic leukemia (CLL). In the primary analysis of ASCEND (median follow-up 16.1 mo), acala showed superior efficacy with an acceptable tolerability profile vs idelalisib (Id) plus rituximab (R) (IdR) or bendamustine (B) plus R (BR) in pts with relapsed/refractory (R/R) CLL (Ghia et al. J Clin Oncol. 2020;38:2849-2861). We report the results of the ASCEND study at ~4 years of follow-up. Methods: In this multicenter, randomized, open-label, phase 3 study (NCT02970318), pts with R/R CLL received oral (PO) acala 100 mg BID until progression or unacceptable toxicity or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or unacceptable toxicity; R: 375 mg/m 2 x1 then 500 mg/m 2 IV [8 total infusions]) or BR (B: 70 mg/m 2 IV; R: 375 mg/m 2 x1 then 500 mg/m 2 IV [6 cycles]). Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed. Results: A total of 310 pts (acala, n=155; IdR, n=119; BR, n=36) were randomized (median age 67 y; del(17p) 15%, unmutated IGHV 74%, Rai stage 3/4 42%). At median follow-up of 46.5 mo (acala) and 45.3 mo (IdR/BR), acala significantly prolonged INV-assessed PFS vs IdR/BR (median not reached [NR] vs 16.8 mo; P<0.0001); 42-mo PFS rates were 62% for acala vs 19% for IdR/BR. In pts with del(17p), median PFS was NR (acala) vs 13.8 mo (IdR/BR; P<0.0001). In pts with unmutated IGHV, median PFS was NR (acala) vs 16.2 mo (IdR/BR; P<0.0001). Median OS was NR in both arms; 42-mo OS rates were 78% (acala) vs 65% (IdR/BR). ORR was 83% (acala) vs 84% (IdR/BR) (ORR + partial response with lymphocytosis: 92% [acala] vs 88% [IdR/BR]). AEs led to drug discontinuation in 23% of acala, 67% of IdR, and 17% of BR pts. Events of clinical interest (acala vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), and grade ≥3 infections (29% vs 29%). Conclusions: At ~4 years of follow-up, acala maintained efficacy compared with standard-of-care regimens and a consistent tolerability profile in R/R CLL. Clinical trial information: NCT02970318. [Table: see text]
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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 | 0.010 | 0.025 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.004 |
| 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 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".