AML: Azacitidin-Venetoclax ist Chemotherapie auch bei fitten Patienten überlegen
核心洞察
The randomized phase II PARADIGM trial found azacitidine plus venetoclax significantly prolonged event-free survival versus intensive induction chemotherapy in previously untreated, induction-eligible AML patients.
Median event-free survival was 14.5 months with azacitidine/venetoclax versus 6.2 months with induction chemotherapy (HR = 0.57; P = .002) at 21.9 months median follow-up.
Grade 3 or higher infections and hemorrhagic events were less frequent with the investigational regimen, and no azacitidine/venetoclax patients died within 30 or 60 days.
Azacitidine plus venetoclax significantly prolonged event-free survival compared with intensive induction chemotherapy in previously untreated patients with acute myeloid leukemia (搜索) (AML) who were eligible for induction therapy, according to results of the randomized phase II PARADIGM trial published in The New England Journal of Medicine.
The investigator-initiated, open-label trial enrolled 172 previously untreated adults with AML at nine U.S. academic centers, all candidates for induction chemotherapy with ECOG performance status 0 to 2. Median age was 64 years and 72% had adverse-risk disease by the 2022 European LeukemiaNet classification. Patients were randomly assigned 1:1 to azacitidine plus venetoclax or induction chemotherapy with a conventional 7+3 cytarabine/anthracycline regimen or CPX-351; those with core-binding-factor fusions or FLT3 (搜索) mutations, and patients younger than 60 years with NPM1 (搜索) mutations, were excluded.
At a median follow-up of 21.9 months, median event-free survival was 14.5 months with azacitidine/venetoclax versus 6.2 months with induction chemotherapy (HR = 0.57; P = .002), and 53% versus 36% of patients were alive without an event at 1 year. Overall response was 88% versus 62%, composite complete remission 78% versus 53%, and 60% versus 40% of patients proceeded to hematopoietic-cell transplantation. Median overall survival was 21.5 months versus 18 months, though the trial was not designed to formally assess overall survival. Grade 3 or higher infections occurred in 28% versus 41% and grade 3 or higher hemorrhagic events in 2% versus 12%; no azacitidine/venetoclax patients died within 30 or 60 days, compared with 30- and 60-day mortality of 3% and 5% with induction chemotherapy. Mean inpatient time over the first 30 days was 12.5 versus 27.3 days, and no patients on the investigational regimen required intensive care versus 10% on induction chemotherapy.
The investigators cautioned that the findings should not be generalized to all patients eligible for intensive therapy, noting that induction chemotherapy remains recommended for fit patients with FLT3 (搜索)-mutated or favorable-risk core-binding-factor AML. Events were assessed by treating investigators without blinded central review, and the study was conducted exclusively at academic centers. The authors concluded the data support azacitidine/venetoclax in fit, transplant-eligible patients with nonfavorable-risk, FLT3-nonmutated AML.