Comparable remission rates in therapy-related and myelodysplasia-related Acute Myeloid Leukemia (AML) versus de novo AML treated with azacitidine and venetoclax: A contemporary real-world study.
Notice bibliographique
Résumé
Abstract Background Patients with secondary acute myeloid leukemia (sAML) have inferior outcomes compared to de novo AML (dn-AML) when treated with intensive chemotherapy. Azacitidine plus venetoclax (Aza-Ven) is increasingly used in patients with sAML due to its improved efficacy and lower treatment-related mortality, which may also serve as a lower-risk effective approach to bridge eligible patients to allogeneic stem cell transplantation. In this study, we aimed to evaluate the outcomes of Aza-Ven in patients with therapy-related AML (t-AML) or myelodysplasia-related AML (AML-MR) at our center. Methods We performed a retrospective study of adults with AML treated with frontline Aza-Ven at the Princess Margaret Cancer Center (Toronto, Canada) between 2017 and 2024. They were categorized into three mutually exclusive groups: t-AML, AML-MR and dn-AML. Patients who previously received cytotoxic therapy or radiotherapy were categorized as t-AML. Patients with prior myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) or with MDS-related gene mutations (MRGM) or cytogenetic abnormalities (MRCA) were categorized as AML-MR. Remaining patients were categorized as dn-AML. Composite complete remission (CRc) was defined as complete remission (CR) and CR with incomplete or partial hematological recovery (CRi/CRh). Overall response rate (ORR) was defined as CRc and morphological leukemia-free state (MLFS). Kaplan–Meier analysis with log-rank tests were used to compare overall survival (OS) between subgroups. Results A total of 132 patients were included: 29 with t-AML, 73 with AML-MR, and 30 with dn-AML. Compared to dn-AML, patients with t-AML had similar age (median 70 vs 76 years, p=0.16), ECOG 0–1 status (74% vs 57%, p=0.26) and non-favorable ELN 2024 risk (52% vs 57%, p=0.79), but more TP53 mutations (29% vs 4%, p=0.03), complex karyotype (CK) (45% vs 13%, p<0.01) and non-favorable ELN 2022 risk (83% vs 53%, p=0.03). CRc rate at any time was 71% vs 69% in patients with t-AML and dn-AML, respectively (p=0.25), including 58% vs 59% after cycle 1 (p=0.25). ORR at any time was 75% vs 86% in patients with t-AML and dn-AML, respectively (p=0.15), including 67% vs 79% after cycle 1 (p=0.11). 60-day mortality was 17% vs 7% in t-AML and dn-AML, respectively (p=0.25). Median OS was 13.1 months in t-AML and 16.0 months in dn-AML, with 24-month OS rates of 29% and 48%, respectively (p=0.30). Within the t-AML subgroup, TP53 mutation (HR 2.67, 95% CI 0.99 – 7.15, p=0.05) and ELN 2022 non-favorable risk (HR 8.07, 95% CI 0.99–65.14, p=0.05) were marginally associated with inferior OS, while CK had a non-significant trend towards inferior OS (HR 1.79, 95% CI, 0.68-4.73, p=0.24). Prior chemotherapy or radiotherapy exposure, non-favorable ELN 2024 and presence of MRGM were not associated with OS in t-AML. Compared to dn-AML, patients with AML-MR had comparable age (median 74 vs 76 years, p=0.36), ECOG 0–1 status (74% vs 57%, p=0.14), and non-favorable ELN 2024 risk (45% vs 57%, p=0.37), but more TP53 mutations (18% vs 4%, p=0.11), CK (32% vs 13%, p=0.04) and non-favorable ELN 2022 risk (97% vs 53%, p<0.01). CRc rate at any time was 65% vs 69% in patients with AML-MR and dn-AML, respectively (p=0.82), including 45% vs 59% after cycle 1 (p=0.11). ORR at any time was 87% vs 86%, in patients with AML-MR and dn-AML, respectively (p=0.92), including 69% vs 79% after cycle 1 (p=0.15). 60-day mortality was 7% in both groups (p=1.00). Median OS was 12.4 months in AML-MR and 16.0 months in dn-AML, with 24-month OS rates of 33% and 48%, respectively (p=0.30). Within the AML-MR subgroup, signaling pathway mutations (FLT3-ITD, NRAS/KRAS) were associated with inferior OS (HR 3.32, 95% CI 1.66-6.63, p<0.01) along with ELN 2024 non-favorable-risk (HR 1.99, 95% CI 1.02–3.90, p=0.04). TP53 mutations were not associated with OS (HR 1.18, 95% CI, 0.52-2.58) along with non-favorable ELN 2022 risk, individual MRGM and CK. Conclusion Patients with sAML in our cohort achieved remission rates comparable to dn-AML with frontline Aza-Ven with non-significant difference in OS. The ELN 2022 and 2024 risk classifications had different prognostic utility between t-AML and AML-MR mostly related to the inclusion of cytogenetic abnormalities in the former and weight of FLT3-ITD and NRAS/KRAS mutations in the latter. Further studies are needed to refine and adapt prognostic classification systems considering the heterogeneity of sAML in patients treated with Aza-Ven.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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) | 0,001 | 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 ».