S145: VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 6-YEAR RESULTS OF THE RANDOMIZED CLL14 STUDY
Bibliographic record
Abstract
Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: One-year fixed-duration venetoclax-obinutuzumab (Ven-Obi) is a standard-of-care for patients with previously untreated chronic lymphocytic leukemia (CLL). The CLL14 study previously demonstrated high efficacy and good tolerability of Ven-Obi in patients with CLL and coexisting conditions. Due to its ongoing follow-up, the CLL14 study provides unique insights into the long-term outcomes of patients after Ven-Obi treatment completion. Aims: The aim of this report is to provide updated efficacy and safety data from the ongoing follow-up of the CLL14 study, all patients being off study treatment for ≥ 5 years. Methods: Patients with previously untreated CLL and coexisting conditions were randomized 1:1 to 12 cycles of venetoclax with 6 cycles of obinutuzumab, or 12 cycles of chlorambucil with 6 cycles of obinutuzumab (Clb-Obi). The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included safety, rates of minimal residual disease (MRD), time to next treatment (TTNT) and overall survival (OS). Follow-up is ongoing. Results: Of the 432 enrolled patients, 216 were randomly assigned to receive Ven-Obi and 216 to receive Clb-Obi. At a median follow-up of 76.4 months (interquartile range 52.5-80.5), PFS remained superior for Ven-Obi compared to Clb-Obi (median 76.2 vs 36.4 months; hazard ratio [HR] 0.40 [95% CI 0.31-0.52], p<0.0001). At 6 years after randomization, the estimated investigator-assessed PFS rate was 53.1% after Ven-Obi, and 21.7% after Clb-Obi. Progressive disease (PD) occurred in 67 cases in the Ven-Obi arm with 39 second-line treatment initiations, and in 141 cases in the Clb-Obi arm (with 103 second-line treatments). TTNT was significantly longer after Ven-Obi (6-year TTNT 65.2% vs 37.1%; HR 0.44, 95% CI 0.33-0.58, p<0.0001). In both arms, the most frequent second-line treatments were BTK inhibitors (61.5% in the Ven-Obi arm, 55.4% in the Clb-Obi arm). The PFS and TTNT difference between the two arms was maintained across all risk groups, including patients with TP53 mutation/deletion (median PFS 51.9 vs 20.8 months; median TTNT 57.3 vs 29.0 months) and unmutated IGHV status (median PFS 64.8 vs 26.9 months; median TTNT 85.4 vs 40.6 months). Multivariate analysis identified TP53 deletion/mutation, unmutated IGHV and lymph node size ≥5 cm as independent negative prognostic factors for PFS in patients treated with Ven-Obi. Five years after treatment completion, 17 (7.9% of the intention-to-treat population) patients in the Ven-Obi arm still had uMRD (<10-4 by NGS in peripheral blood), 22 (10.2%) had low (L)-MRD (≥ 10-4 and < 10-2) and 23 (10.6%) high (H)-MRD (≥ 10-2), compared to 4 (1.9%) uMRD, 9 (4.2%) L-MRD and 18 (8.3%) H-MRD in the Clb-Obi arm. Overall, 48 deaths were reported in the Ven-Obi arm (9 PD related) and 70 in the Clb-Obi arm (26 PD related); at 6-year-OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR 0.69 [0.48-1.01], p=0.052). Second primary malignancies were reported in 30 patients in the Ven-Obi and 18 in the Clb-Obi arm; cumulative incidences 6 years after randomization were 14.2% and 8.5%, respectively (p=0.071). Two Richter transformations were reported in the Ven-Obi arm and four in the Clb-Obi arm. No new safety signals were observed. Summary/Conclusion: These data confirm a long-term PFS benefit of fixed-duration Ven-Obi treatment compared to Clb-Obi, including patients with high-risk CLL. Five years after completing Ven-Obi, over half of patients remained in remission, and over 60% had not required second-line treatment. The 1-year Ven-Obi regimen is an effective fixed-duration option for patients with CLL and coexisting conditions.Keywords: Obinutuzumab, Venetoclax, B-CLL, Chronic lymphocytic leukemia
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".