134 | EFFICACY AND SAFETY OF FIRST‐LINE IBRUTINIB PLUS VENETOCLAX IN PATIENTS WITH MANTLE CELL LYMPHOMA (MCL) WHO WERE OLDER OR HAD TP53 MUTATIONS IN THE SYMPATICO STUDY
Bibliographic record
Abstract
NCT03112174 Introduction: The phase 3 SYMPATICO study evaluated ibrutinib (Ibr) combined with venetoclax (Ven) in 3 cohorts of patients with MCL: an open-label safety run-in phase to evaluate concurrent initiation of IbrþVen in relapsed/refractory (R/ R) MCL; a randomized phase to evaluate IbrþVen versus Ibrþplacebo (Pbo) in R/R MCL; and an open-label cohort to evaluate first-line IbrþVen in treatment-naive (TN) MCL.Primary analysis of the randomized phase showed superior progression-free survival (PFS) with IbrþVen versus IbrþPbo in patients with R/R MCL (Wang M et al.Lancet Oncol.2025).Here, we report efficacy and safety of IbrþVen in patients with TN MCL in older patients (≥ 65 years) or younger patients with a TP53 mutation (TP53mut) (≥ 18 years) who are in need of novel and better tolerated treatment options.Methods: Older patients (≥ 65 years) or patients with a TP53mut with TN MCL received oral Ibr 560 mg once daily and Ven (5-week ramp-up to 400 mg once daily) for 2 years, then single-agent Ibr 560 mg until progressive disease (PD) or unacceptable toxicity.The primary endpoint was complete response (CR) rate assessed by investigator per Lugano criteria.Key secondary endpoints included overall response rate (ORR), duration of response (DOR), PFS, overall survival (OS), and time to next treatment.Subgroup analyses were performed according to TP53mut status and age.Results: In total, 78 patients with TN MCL were enrolled.At baseline, 83% of patients were ≥ 65 years, 97% had Eastern Cooperative Oncology Group performance status of 0-1, 45% had high-risk simplified MCL International Prognostic Index score, 31% had bulky disease (≥ 5 cm), 78% had bone marrow involvement, 46% had splenomegaly, and 37% had TP53mut.Median time on study was 40.5 months (range, 0.6þ-46.9).The CR rate was 69% (95% CI: 58-79), and the ORR was 95% (95% CI: 87-99).Median DOR was 37.1 months (95% CI: 30.3-NE).Median PFS was 40.2 months, and 3-year OS was 79%.The CR rate was 76% in patients ≥ 65 years without TP53mut, 44% in patients ≥ 65 years with TP53mut, and 73% in patients < 65 years with TP53mut; median PFS was 40.2, 22.0, and 15.4 months, and 3-year OS was 85%, 66%, and 73%, respectively (Table ).Median duration of treatment was 24.0 months (range, 0.3-46.9).Most common adverse events (AEs) were diarrhea (49%), fatigue (37%), neutropenia (35%), and COVID-19 (32%).The most common grade ≥ 3 AE was neutropenia (29%).Conclusions: First-line IbrþVen showed promising efficacy with high CR rates and durable remissions in patients with TN MCL with and without TP53mut.Safety was acceptable and trended better in younger patients.IbrþVen may be an option for older patients with TN MCL or patients of any age with TP53mut.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".