IBRUTINIB VS TEMSIROLIMUS: THREE‐YEAR FOLLOW‐UP OF PATIENTS WITH PREVIOUSLY TREATED MANTLE CELL LYMPHOMA FROM THE PHASE 3, INTERNATIONAL, RANDOMIZED, OPEN‐LABEL RAY STUDY
Bibliographic record
Abstract
Introduction: Ibrutinib (IBR), a first-in-class, once-daily, oral, covalent inhibitor of Bruton's tyrosine kinase, is highly active in relapsed/refractory (R/R) MCL. The phase 3, randomized, open-label RAY study compared IBR with temsirolimus (TEM) in patients (pts) with R/R MCL and ≥1 prior rituximab-containing therapy. At median 20.0 month follow-up, IBR was superior to TEM for independent review committee-assessed progression-free survival (PFS) (HR: 0∙43; 95% CI: 0∙32-0∙58; p < 0.0001) (Dreyling et al. Lancet 2016). Here, we present 3-year follow-up results (end of study). Methods: 280 pts were randomized 1:1 to oral IBR (560 mg once-daily; n = 139) or IV TEM (175 mg: days 1, 8, 15 of C1; 75 mg: days 1, 8, 15 of subsequent cycles; n = 141) until disease progression/unacceptable toxicity. Long-term efficacy was investigator-assessed. Results: At a median follow-up of 39 months (mos) for IBR and TEM, respectively, median PFS was 15.6 mos vs 6.2 mos (HR [95% CI], 0.45 [0.35-0.60]; p < 0.0001) (Figure 1A); median PFS for pts with only 1 prior line of therapy (LOT) was 25.4 mos (IBR) vs 6.2 mos (TEM) (HR: 0.40; 95% CI: 0.25-0.64) (Figure 1B). Overall response rate (ORR) was 77.0% (IBR) vs 46.8% (TEM); CR rate was 23.0% vs 2.8% (p < 0.0001). ORR for pts with 1 prior LOT was 75.4% (IBR) vs 52.0% (TEM); CR rate was 33.3% vs 4.0%. Median duration of response was 23.1 mos (IBR) vs 6.3 mos (TEM). Median time to next treatment was 31.8 mos (IBR) vs 11.6 mos (TEM) (HR [95% CI], 0.33 [0.24-0.46]; p < 0.0001). PFS2 was 26.2 mos (IBR) vs 15.4 mos (TEM) (HR [95% CI], 0.67 [0.50-0.90]; p < 0.0079). With 39% of pts randomized to TEM crossing over to IBR, median overall survival (OS) was 30.3 mos (IBR) vs 23.5 mos (TEM) (HR: 0.74; 95% CI: 0.54-1.02; p = 0.0621) (Figure 1C); median OS for pts with 1 prior LOT was 42.0 mos (IBR) vs 27.0 mos (TEM) (HR: 0.75; 95% CI: 0.43-1.30) (Figure 1D). Median treatment duration was 14.4 mos (IBR) vs 3.0 mos (TEM), with 24% of IBR pts and 0 TEM pts on treatment at study end. Despite differences in exposure, overall frequency of adverse events (AEs) was lower with IBR vs TEM. AEs leading to treatment discontinuation: 17.3% (IBR) vs 31.7% (TEM). Most common treatment-emergent AEs: diarrhea, fatigue, cough (IBR) and thrombocytopenia, anemia, diarrhea (TEM). Grade ≥ 3 AEs: 74.8% (IBR) and 87.1% (TEM). Serious AEs: 56.8% (IBR) and 59.7% (TEM). Keywords: ibrutinib; mantle cell lymphoma (MCL); temsirolimus.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".