Real-world evidence evaluation of the safety and efficacy of intensive chemotherapy with or without gemtuzumab ozogamicin (GO) in patients with newly diagnosed Acute Myeloid Leukemia (AML) and favorable or intermediate risk cytogenetics
Notice bibliographique
Résumé
Abstract Introduction Gemtuzumab ozogamicin (GO) is approved for use in combination with cytarabine plus daunorubicin (7+3) for the treatment of de novo acute myeloid leukemia (AML) with favorable or intermediate risk cytogenetics. This study aimed to describe real-world evidence comparing the safety and efficacy of 7+3 alone or with GO in patients (pts) with AML. Patients and methods This retrospective study included adult pts with AML and favorable/intermediate risk cytogenetics who received 7+3 induction alone or with GO at the Princess Margaret Cancer Center (Toronto) from October 1st 2018 to October 1st 2024. GO was dosed at 3 mg/m2 on days 1, 4 and 7 with 7+3 per the ALFA-0701 protocol. Endpoints included composite complete remission (CRc) rates, measurable residual disease (MRD) negativity rates, overall survival (OS) and relapse-free survival (RFS) with analysis of key genetic subgroups (core binding factor [CBF], NPM1-mutated [NPM1mut], intermediate-risk cytogenetics without NPM1mut [INT]). Propensity score matching with inverse probability treatment weighting (IPTW) compared outcomes with 7+3 vs 7+3+GO, matching for age, sex, ECOG, WBC, NPM1mut and CBF-AML. Veno-occlusive disease (VOD), bleeding, and hepatotoxicity were adverse events (AEs) evaluated with severity graded by CTCAE v5.0. Results In total, 162 pts were included, 62 received 7+3+GO and 100 received 7+3. Median age was 58 years (range, 22-85), 51% were male, 85% had ECOG of 0-1 and median WBC was 9.0 x 109/L (range, 0.5 – 288.0), with no differences between groups. Twenty-six (42%) pts who received 7+3+GO had CBF AML (15 [24%] t(8;21), 11 [18%] inv(16)), vs 10 (10%) pts who received 7+3 (3 [3%] t(8;21), 7 [7%] inv(16)) (p<0.05). Twenty-eight (45%) pts who received 7+3+GO had intermediate-risk cytogenetics vs 81 (81%) pts who received 7+3 (p<0.05), including 14 (23%) and 45 (45%), respectively, without NPM1mut (INT). In pts who received 7+3+GO, 17 (27%) had NPM1mut AML vs 41 (41%) in pts who received 7+3 (p=0.20). CRc was achieved in 56 (90%) pts with 7+3+GO and in 77 (77%) pts with 7+3 (p<0.05). CRc rates were similar within each genetic subgroup: 96% vs 100% (CBF); 88% vs 90% (NPM1mut); and 57% vs 51% (INT) for pts who received 7+3+GO vs 7+3, respectively. MRD negativity by flow cytometry was achieved in 46 (81%) vs 58 (58%) in pts after 7+3+GO and 7+3, respectively (p<0.05). MRD negativity rates were not significantly different within each genetic subgroups: 92% vs 80% (CBF, p=0.30); 65% vs 73% (NPM1mut, p=0.54); and 57% vs 42% (INT, p=0.54) for pts who received 7+3+GO vs 7+3, respectively. With a median follow-up of 28.6 months (7+3+GO) and 44.1 months (7+3), the 2-year OS was 78% (95% CI, 68-90) and 64% (95% CI, 55-75), respectively, (HR, 0.71, 95% CI 0.38-1.33, p=0.29). In pts with inv(16) AML, the 2-year OS was 91% (95% CI, 75-100) with 7+3+GO and 86% (95% CI, 63-100) with 7+3 (p=0.87). In pts with t(8;21) AML, the 2-year OS was 66% with 7+3+GO and 3/3 pts with 7+3 were alive at last follow-up. In pts with INT AML, the 2-year OS was 78% (95% CI, 59-100) with 7+3+GO vs 58% (95% CI, 44-76) with 7+3 (p=0.40). In pts with NPM1mut AML, the 2-year OS was 74% (95% CI, 54-100) with 7+3+GO and 70% (95% CI, 57-86) with 7+3 (p=1.00). Among patients achieving CRc, the 2-year RFS was 68% (95% CI, 56-83) with 7+3+GO and 65% (95% CI, 55-77) with 7+3 (p=1.00). There were no significant differences in 2-year RFS between pts who received GO or not within each pre-specified subgroup. The frequency of AEs was higher in pts treated with 7+3+GO: VOD 4 (6%) vs 0 (0%); grade 3-4 AST/ALT elevation 9 (15%) vs 10 (10%); and grade 3-4 bleeding 15 (24%) vs 11 (11%). Grade 5 bleeding was reported in 3 (5%) and 1 (1%) pts, respectively. The 60-day mortality rate was 7% both with 7+3+GO and with 7+3 (p=1.00). With propensity score matching with IPTW, 2-year OS was 81% (95% CI, 71-92) with 7+3+GO and 68% (95% CI, 59-79) with 7+3 (p=0.39), (HR 0.73, 95% CI 0.36-1.5, p=0.39). The 2-year RFS was 73% (95% CI, 60-87) and 69% (CI 95%, 58-81) with 7+3+GO and 7+3, respectively. Conclusion Within key subgroups of AML (CBF, NPM1mut and INT), the use of GO did not result in significant improvements in CRc, MRD negativity rates and survival outcomes in this retrospective study. VOD, liver enzymes elevation, and bleeding were more frequent with GO. Further research, including larger sample size is needed to identify pts who benefit from GO and to optimize clinical outcomes.
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 | 0,020 | 0,046 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,006 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».