DP044 | PRELIMINARY ANALYSIS OF CLL-ZANU2024, AN ITALIAN NON-INTERVENTIONAL STUDY ASSESSING THE REAL-WORLD USE OF ZANUBRUTINIB IN THE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Bibliographic record
Abstract
The CLL-ZANU2024 study is an Italian, observational, multicenter, longitudinal secondary data analysis evaluating the safety and efficacy of Zanubrutinib in real-world post-marketing setting. It retrospectively examines chronic lymphocytic leukemia (CLL) patients who initiated Zanubrutinib from October 2023, regardless of prior treatment. The study aimed to enroll patients (pts) across 56 Italian sites, providing the first Italian real-world data register on Zanubrutinib in CLL. The primary end-point was time to treatment discontinuation (TTD) and reasons for discontinuation; the secondary end-point was time to next treatment or death (TTNTD). As of May 2024, 393 pts were included. Median age was 76 years (range 44-94), and 63.2% were male. Zanubrutinib was first-line treatment in 237 pts (60.3%) (treatment-naïve, TN) and subsequent-line therapy in 156 pts (39.7%) (refractory/relapsed, RR). At treatment start, Binet stage was: A in 10.4%, B in 38.4%, C in 51.1%. Del(17p), TP53 mutation, and IGHV status were available in 91.1%, 90.8%, and 87.8% of pts, respectively. Del(17p) was detected in 16.5% (31 TN, 28 RR), TP53 mutations in 20.2% (36 TN, 36 RR), and IGHV was unmutated in 70.1% (154 TN, 88 RR). Among 348 pts with both del(17p) and TP53 data, concomitant abnormalities were observed in in 9.5%, del(17p) only in 6.9%, and TP53-mutation only in 10.6%. Bulky lymph nodes (>10 cm) were observed in 6.4%. Most pts (75.8%) received an initial zanabrutinib dose of 320 mg/day, as per Summary of Product Characteristics (SmPC). At a median follow-up of 8 months (range 1-32) median TTD was not reached in the entire cohort nor in TN and RR subgroups (Figure 1A). The 12-month discontinuation rate was 10.6% overall (9.3% TN, 12.8% RR). Overall, 7.6% (30/393) of patients (18 TN, 12 RR) discontinued treatment. Main reasons were toxicity (15 pts) and disease progression (10 pts). Patients with a Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (CFS) >3 had a significantly higher probability of discontinuating therapy (12-month discontinuation rate CFS < or =3 vs CFS>3: 6.2% vs 22.3%, P<0.0001) (Figure 1B), while IGHV status and TP53 disruption did not significantly impact on TTD. The 12-month TTNTD probability was 94.6% overall (95.8 % TN, and 92.5% RR). This preliminary report from the largest available real-world study on zanubrutinib in CLL confirms a favorable safety profile in both TN and RR settings, with a low rate of discontinuation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".