Indolent lymphoma: Bendamustine, rituximab and acalabrutinib in Waldenstroms Macroglobulinemia (BRAWM)
Notice bibliographique
Résumé
Background: Waldenström’s macroglobulinaemia (WM) is an uncommon lymphoproliferative disorder. Many options are available, however, an optimal first-line therapy for WM has not be defined. We postulated that combining bendamustine and rituximab (BR) with a next generation BTK inhibitor would result in deeper responses as measured by complete response (CR) and very good partial response (VGPR) rates, and provide a longer duration of response. Objectives: The primary objective of this trial is to document the CR and VGPR rates Methods: The BRAWM clinical trial combines BR with acalabrutinib in a fixed duration treatment course including six cycles of BR and 12 months of acalabrutinib. This trial is taking place at 8 clinical sites across Canada and 33 patients have been enrolled, with a recruitment goal of 59. Results: A pre-defined interim analysis of the first 30 enrolled patients showed; median age of patients was 66; 25 were male; two patients were low risk, 14, intermediate and 15 high risk. Seventeen patients completed combination therapy, 9 completed monotherapy and 2 were followed-up at 18 months (6 months post therapy). Clinical results to date: Two patients discontinued treatment early; 1 at cycle 7 (with a VGPR) but experienced an adverse event requiring treatment; 1 at cycle 3 with possible disease progression. There were 186 treatment related adverse events (TRAEs) among 25 of 30 participants; 5 participants did not experience a TRAE; 163 of these occurred during combination therapy; 23 during monotherapy in 7 of 17 participants, where 10 participants did not experience a TRAE. During combination therapy, 16 of the 163 TRAE’s were grade 3; neutropenia (n = 8), including 2 that were febrile neutropenia, n = 1 for each: atrial fibrillation, transaminitis, cellulitis, fatigue and pulmonary emphysema. An additional five were also considered serious and included febrile neutropenia (n = 2), and n = 1 for each fever, allergic reaction and bowel obstruction. During monotherapy, there were no serious TRAEs. There were 2 grade 3 events during monotherapy in two different patients; decreased neutrophil count, and syncope. There were 21 dose interruptions in 11 participants, all but one of whom returned to regular dosage. Of assessed patients, 20/20 have MyD88 mutations, 4/20 have a CXCR4 mutation, and none had a TP53 mutation. Minimal residual disease (MRD) analysis using next generation sequencing of the IgV regions will be reported. Conclusions: Bendamustine, rituximab and acalabrutinib front-line therapy for WM is safe and well tolerated and initial clinical results show that this treatment induces a high percentage of VGPRs. The research was funded by: AstraZeneca Keywords: Combination Therapies, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. N. L. Berinstein Consultant or advisory role: AstraZeneca Research funding: AstraZeneca, Merck, IMV N. Forward Honoraria: AstraZeneca, AbbVie, BeiGene, Celgene/BMS, IMV, Kite, Janssen, Pfizer, Roche, Servier Research funding: Astellas, AstraZeneca, IMV, Merk, MorphoSys, Seattle Genetics, Roche Other remuneration: Speaker Fees: Pfizer, BeiGene, AstraZeneca M. Shafey Consultant or advisory role: Jansen, Roche Canada, Kite/Gilead, Novartis, BeiGene, Incyte, Abbvie, BMS, AstraZeneca A. Nikonova Consultant or advisory role: Forus, Janssen, Astra Zeneca, Apotex, Incyte Educational grants: Janssen D. MacDonald Honoraria: Abbvie, Astra Zeneca, Beigene, BMS, Incyte, Kite Gilead, Roche, and Seattle Genetics D. Villa Consultant or advisory role: AZ, BeiGene, Janssen, Roche, Kite/Gilead, Merck, BMS/Celgene, ONO Pharmaceuticals. Honoraria: AZ, BeiGene, Janssen, Roche, Kite/Gilead, Merck, BMS/Celgene, ONO Pharmaceuticals. Research funding: Roche, AstraZeneca I. Sandhu Honoraria: Celgene/BMS, Kite/Gilead, Janssen, Sanofi, FORUS, Pfizer M. Aljama Consultant or advisory role: Jansen, Sanofi, Pfizer, Beigene J. Larouche Consultant or advisory role: Incyte, Gilead Research funding: Incyte, Astra-Zeneca, Genmab
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,001 |
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 ».