Efficacy, Toxicity and Cost of Venetoclax-Based Combinations for the Treatment of Acute Myeloid Leukemia: Real-World Evidence from a Canadian Academic Center
Notice bibliographique
Résumé
Abstract Introduction: Venetoclax (ven) in combination with azacitidine (aza) or low-dose cytarabine (LDAC) has demonstrated efficacy for the first-line treatment of acute myeloid leukemia (AML) patients who are deemed unfit for intensive induction chemotherapy. The efficacy of ven-based treatment for relapsed or refractory (r/r) AML has not been prospectively evaluated. We have used off-label ven-based combinations to treat r/r AML patients and de novo AML in otherwise fit patients to avoid prolonged hospitalization. The objective of this study was to review the efficacy, toxicity and medication costs associated with ven-based treatments for AML in a Canadian university hospital. Methods: After local IRB approval, we conducted a retrospective chart review of all patients who received ven-based treatments, outside of a clinical trial, for AML at Hopital Maisonneuve-Rosemont. Supportive care included tumor lysis syndrome (TLS) prophylaxis, antiviral, antifungal and antibacterial prophylaxis. Results: 40 patients received 41 ven-based treatments between November 2017 and July 2021. Most patients had r/r AML (n=25, including 17 in first relapse after allogeneic hematopoietic cell transplantation), while 16 patients had de novo AML (10 deemed fit for intensive chemotherapy). Median age was 62 years old. Median duration of ven-based treatment was 4 cycles and median follow-up was 140 days after ven initiation. Ven-aza was used for 33 patients. ven-LDAC was used for the first 7 patients. One patient received ven-gilteritinib. Posaconazole was the main antifungal agent used, with ven dose reduced to 70 mg daily (25 patients). The complete remission (CR) and CR with incomplete hematological recovery (CRi) rate was 46%, higher for de novo vs r/r AML (56% vs 40%). Most patients achieved blast clearance with treatment: CR+CRi+morphologic leukemia-free state (MLFS) rate 63% (75% de novo and 56% r/r). Median overall survival was 258 days (376 days for ven-aza treated patients). All 8 patients (de novo n=5, r/r n=3) with NPM1 or IDH1/2 mutations achieved blast clearance (CR+CRi 87%), while 22 patients with adverse-risk AML as defined by 2017 ELN risk stratification had a lower yet respectable response rate (CR+CRi 36%). Ven-LDAC had no activity in advanced disease, with no response for 6 r/r patients who all had adverse-risk AML, and is no longer used in our institution. The majority of patients were able to receive treatment on an outpatient basis after a brief hospital stay during ven ramp-up. Five patients remained hospitalized for the entire first cycle. Four patients died from infectious causes during the first cycle (2 unfit patients with first line ven-aza, 2 r/r patients with ven-LDAC). Two cases of suspected TLS requiring treatment delays occurred, with no clinical TLS. Venetoclax dose reductions for hematological toxicity were frequently required (51% for all patients, 73% of patients that achieved a response to ven). The average medication cost per cycle of ven-aza was 4 394 $ CAN and was 6 765 $ CAN per cycle for ven-LDAC. Conclusion: In this retrospective real-life review, ven-based treatment produced response rates in line with published prospective evidence among de novo AML patients, and a very clinically meaningful response rate for r/r AML, where therapeutic options are limited and outcomes with conventional chemotherapy dismal. The presence of NPM1 or IDH1/2 mutations was predictive of high response rates. Dose reductions were often required for cytopenias but non-hematological toxicities were limited. Although associated with significant cost, ven-aza represents a safe and effective treatment option for r/r AML which can successfully be delivered in an ambulatory setting. Figure 1 Figure 1. Disclosures Bouchard: Otsuka: Consultancy; Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy. Bambace: AbbVie: Consultancy; Excelthera: Research Funding; Kiadis: Research Funding. Bernard: Kiadis: Research Funding; Excelthera: Research Funding; BMS: Consultancy; Taiho: Consultancy. Hebert: BMS-Celgene: Research Funding. Bergeron: Jazz Pharmaceuticals: Consultancy; Amgen: Consultancy; Servier: Consultancy; BMS: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy. OffLabel Disclosure: Venetoclax to treat relapsed or refractory acute myeloid leukemia
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,006 | 0,016 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,002 | 0,005 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,002 | 0,000 |
| Science ouverte | 0,002 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 source (Gemma direct ou Codex distillé), 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 ».