IBRUTINIB IN ASSOCIATION WITH R‐DHAP/OX FOR PATIENTS WITH RELAPSED/REFRACTORY B‐CELL LYMPHOMA: PRELIMINARY RESULTS OF THE BIBLOS PHASE IB LYSA STUDY
Bibliographic record
Abstract
Introduction: Ibrutinib (Ibru), an inhibitor of Bruton's tyrosine kinase, is efficient, in monotherapy, for treatment of relapsed or refractory (R/R) mantle cells lymphoma and R/R chronic lymphocytic leukemia (Wang, 2013). The safety and activity of Ibru in combination with R-CHOP or R-Benda has also been evaluated (Younes, 2014; Maddocks 2015). We conducted a phase Ib study to assess of the safety of ibru associated with R-DHAP or R-DHAOx for patients (pts), with R/R B-cell lymphoma candidates for autologous stem cell transplantation (ASCT). Methods: Pts were planned to receive 3 cycles, every 21 days, of rituximab, dexamethasone, cytarabine and cisplatin (R-DHAP) or oxaliplatin (R-DHAOx) in association with escalating doses of ibru given on D1 to D21. Dose level (DL) 1 was 420 mg/day. The dose-variation scheme followed a “3 + 3” design (DL-1: 280 mg/day; DL2: 560 mg/day). Dose-limiting toxicities (DLTdefined as: non-hematological toxicity grade (Gr) 3–4 excluding alopecia, diarrhea and/or nausea/vomiting and/or fatigue/asthenia for <7 days, any Gr ≥ 2 hemorrhagic events, any Gr ≥ 1 intracranial hemorrhage and any Gr ≥ 4 hematological toxicity >7 days) were considered during the first cycle. DLT. Results: Between 05/14 and 07/15, 25 pts were treated (R-DHAP: 13, 1 non evaluable; R-DHAOx: 12). In the DL1 cohort, DLTs related to ibru were observed in 3/6 pts receiving R-DHAOx (Gr3 cutaneous eruption, Gr3 febrile neutropenia and infection, Gr4 thrombocytopenia) and in 3/6 pts receiving R-DHAP (Gr4 cutaneous eruption, Gr4 thrombocytopenia and Gr4 sepsis). A total of 13 pts were treated at DL-1 with 1 pt experiencing DLT in each cohort (R-DHAP group: Gr4 thrombocytopenia and Gr4 gastric hemorrhage, Gr3 atrial fibrillation; R-DHAOx group: Gr3 epigastric pain). 6 (50%) pts treated with ibru at the dose of 420 mg and 10 (77%) of those treated at the dose of 280 mg received more than 80% of the planned dose. All pts experienced ≥1 adverse events (AE) and Gr3–4 hematological AEs (neutropenia: 17 pts; thrombocytopenia: 25 pts). Overall, 3 pts presented serious hemorrhagic AE, 4 developed cutaneous eruptions. 1 died (cardiac toxicityassessed as unrelated to ibru). Ibru was discontinued in 9 pts (7 for toxicities or DLTs, and 2 due to pt's decision). Response to treatment was evaluable in 16 pts (64%) and14 responded to the treatment (8 (50%) CR and 6 (37%) PR. Stem cells were harvested in 16 pts and all of them underwent ASCT (CD34+ cells >3.0 × 106/kg in 94% of the collected pts after 1 sole apheresis). Conclusions: Preliminary results show that the R-DHAP/Ox plus ibru. (given from D1 to D21) regimen led to several DLTs. Since underdosing (280 mg) might not optimal to achieve an optimal response, a new dose escalation phase with ibru given only from D5 to D18 with pharmacokinetics analyses was performed. The results of this will be presented. Expansion phase will open for inclusion in a few weeks. Keywords: autologous stem cell transplantation (ASCT); B-cell lymphoma; ibrutinib.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".