IBRUTINIB IN ASSOCIATION WITH R‐DHAP/OX FOR PATIENTS WITH RELAPSED/REFRACTORY B‐CELL LYMPHOMA: PRELIMINARY RESULTS OF THE BIBLOS PHASE IB LYSA STUDY
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».