P648: REAL-WORLD TREATMENT AND OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) RECEIVING FIRST-LINE (1L) THERAPY IN THE NOVEL AGENT ERA: AN INTERNATIONAL STUDY
Bibliographic record
Abstract
Background: An expansion of treatment options in CLL makes it important to understand contemporary practice and treatment effectiveness. However, real-world data are still emerging regarding outcomes among different therapeutic options. Aims: The study goal was to describe treatment patterns and clinical outcomes of patients (pts) receiving 1L CLL treatment in real-world settings. Methods: Twenty three centers of the CLL Collaborative Study of Real-World Evidence (CORE), an international, retrospective, observational study, provided data for this analysis. Pts diagnosed with CLL/SLL were included if they were ≥18 years at diagnosis and initiated 1L therapy on/after 01/01/2014 and excluded if they participated in a clinical trial. Descriptive analyses were conducted to characterize pt demographics and clinical characteristics. Outcomes, including time to next treatment or death (TTNT-D) and progression-free survival (PFS), were estimated via the Kaplan-Meier (KM) method for the overall population and those with high-risk cytogenetics (del(17p)/TP53 and IGHV unmutated) or age ≥65. Results: Of 1,244 pts included in the study, between 2014-2022, 39% initiated CT/CIT in 1L (eg, bendamustine-rituximab [BR, 16%]; fludarabine-cyclophosphamide-rituximab [FCR, 9%]; obinutuzumab-chlorambucil [GClb, 5%]), 9% anti-CD20 monotherapy (eg, rituximab, 6%; obinutuzumab, 2%), 45% BTKi-based therapy (eg, ibrutinib, 42%; acalabrutinib, 3%), 7% venetoclax (Ven)-based therapy (eg, venetoclax-obinutuzumab [V+G, 5%]; venetoclax-rituximab [V+R, 1%]; venetoclax monotherapy, 1%), and 1% initiated other therapies over a median follow-up of 13-34 months. The median age was 63 years at diagnosis and 66 years at 1L initiation; 66% of pts were males, 35% had unmutated IGHV, and 15% had del(17p)/TP53, though 32-53% were not tested for IGHV and 10-18% for genetic mutations. Overall, the median TTNT-D (mTTNT-D) was 35, 18, 43 months for pts who received 1L therapy with CT/CIT, anti-CD20, and BTKi, respectively; mTTNT-D was not reached for Ven-based therapy over a median follow-up of 13 months. KM estimates of TTNT-D at month 24 were 64%, 42%, 69%, and 88% for CT/CIT, anti-CD20, BTKi, and Ven-based therapy, respectively (Table1). Trends were similar in subgroups: del(17p)/TP53, IGHV unmutated, or age ≥65. The median PFS (mPFS) was 39, 23, 51 months for pts who received CT/CIT, anti-CD20, and BTKi, respectively; mPFS was not reached for Ven-based therapy. KM estimates of PFS at month 24 were 67%, 48%, 80%, and 88% for CT/CIT, anti-CD20, BTKi- and Ven-based therapy, respectively (Table1). Similar trends were seen in subgroups: del(17p)/TP53, IGHV unmutated, or age ≥65. Patients categorized into the ‘other’ treatment group were not assessed due to low sample size (n=11; 1%).Summary/Conclusion: Our study presents contemporary practice and outcomes in CLL. We observed that almost 50% of pts were treated in the front-line setting with anti-CD20 monotherapy or CT/CIT despite availability of targeted agents. The continued use of anti-CD20 monotherapy and CT/CIT is surprising in the era of novel agents. Pts initiating 1L therapy with anti-CD20 or CT/CIT experienced worse clinical outcomes, providing further evidence of the effectiveness afforded by novel agents in 1L. Although mTTNT-D and mPFS were not reached for Ven-based therapy perhaps due to shorter follow-up, KM estimates tended to be higher through month 24, especially for high-risk and older pts. As the treatment paradigm continues to evolve, future exploration with larger cohorts and longer follow-up time should be undertaken. Keywords: Progression, Chemotherapy, Targeted therapy, Clinical outcome
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".