VENCLYXTO in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.
*VIALE-A was a randomised (2:1), double-blind, placebo-controlled, Phase 3 study that evaluated the efficacy and safety of VENCLYXTO plus AZA in patients with newly diagnosed AML who were ineligible for intensive chemotherapy. The median overall survival with VENCLYXTO plus AZA was 14.7 months (95% CI: 11.9-18.7) vs 9.6 months for AZA alone (95% CI: 7.4-12.7; HR=0.66; P<0.001).1
VENCLYXTO + AZACITIDINE
test
VIALE-A: A PHASE 3 TRIAL COMPARING VENCLYXTO PLUS AZA VERSUS AZA ALONE IN FIRST-LINE AML TREATMENT1,2
A randomised, double-blind, placebo-controlled study that evaluated the efficacy and safety in patients ineligible for intensive chemotherapy1,2
SELECT INCLUSION CRITERIA2
KEY ELIGIBILITY:
| • | ≥18 years and confirmed AML by World Health Organization criteria, previously untreated |
| • | Ineligible for induction therapy due ≥75 years of age or ≥18 to 74 years of age with comorbidities |
| • | ECOG status of 0 to 2 for patients ≥75 years of age or 0 to 3 for patients ≥18 to 74 years of age |
SELECT EXCLUSION CRITERIA2
KEY INELIGIBILITY:
| • | Patients who have previously received any HMA, VENCLYXTO, or chemotherapy for myelodysplastic syndrome |
| • | Patients with core-binding factor AML |
| • | Patients who had favourable risk cytogenetics such as t(8;21), inv(16), t(16;16), or t(15:17) |
EFFICACY AND SAFETY WERE EVALUATED IN NEWLY DIAGNOSED PATIENTS WITH AML WHO WERE INELIGIBLE FOR INDUCTION CHEMOTHERAPY1
Treatment was continued until disease progression or unacceptable toxicity was observed1
A BROAD RANGE OF PATIENT SUBGROUPS WERE STUDIED1,2
Baseline demographic and disease characteristics were similar between the treatment arms1,2
*The dual primary efficacy endpoints of the study were overall survival, measured from the date of randomisation to death from any cause, and composite complete remission rate (CR+CRi).1
VENCLYXTO PLUS AZA SIGNIFICANTLY EXTENDED MEDIAN OVERALL SURVIVAL VERSUS AZA ALONE IN HARD-TO-TREAT PATIENT POPULATIONS1*
VENCLYXTO plus AZA demonstrated a 5.1-month increase in median overall survival vs AZA alone (14.7 months vs 9.6 months, respectively [95% CI: 0.52-0.85])1
MEDIAN OVERALL SURVIVAL
VENCLYXTO plus AZA demonstrated a 50% increase in median overall survival vs AZA alone1
THE INCREASED OVERALL SURVIVAL SEEN WITH VENCLYXTO PLUS AZA IN THE OVERALL PATIENT POPULATION WAS CONSISTENT ACROSS PATIENT SUBGROUPS1
FOREST PLOT OF OVERALL SURVIVAL
*“Hard-to-treat patient populations” refer to those patients who are ineligible for intensive chemotherapy.
†Hazard ratio estimate (VENCLYXTO plus AZA vs AZA alone) is based on Cox proportional hazards model stratified by cytogenetics (intermediate risk, poor risk) and age (18-<75, ≥75) as assigned at randomisation; P value based on log-rank test stratified by the same factors.1
‡Overall survival in FLT3 and IDH1/2 subgroups were prespecified secondary endpoints. Overall survival in FLT3 did not meet statistical significance and does not support conclusions on efficacy. Other biomarker subgroups (TP53 and NPM1) and cytogenetic risk were prespecified exploratory endpoints.1
§ECOG status does not correlate with eligibility.
STATISTICALLY SIGNIFICANT DIFFERENCES IN REMISSION VS AZA ALONE WERE ACHIEVED1,2
VENCLYXTO plus AZA more than DOUBLED the remission rate vs AZA alone1,2
COMPOSITE REMISSION RATES (CR+CRi)
VENCLYXTO plus AZA almost TRIPLED the MRD response† rate in patients who achieved remission (CR+CRi) vs AZA alone1
MRD RESPONSE RATES
†CR+CRi MRD response rate is defined as the percentage of patients achieving a CR or CRi and demonstrating an MRD response of <10-3 blasts in bone marrow as determined by a standardised, central multicolour flow cytometry assay.1
Almost one quarter of patients who achieved remission (CR+CRi) with VENCLYXTO plus AZA had an MRD response (23% vs 8% for AZA alone)1
GREATER CR+CRi* IMPROVEMENT VS AZA ALONE WAS SEEN ACROSS GENOMIC RISK AND MUTATION SUBGROUPS IN HARD-TO-TREAT PATIENTS1,2‡
More than half of patients achieved remission with VENCLYXTO plus AZA across mutation subgroups1,2
COMPOSITE REMISSION RATES (CR+CRi) BY MUTATION
SIGNIFICANT INCREASE IN REMISSION RATES (CR+CRi)
VENCLYXTO plus AZA increased remission rates across mutation subgroups vs AZA alone by:1,2
THE MAJORITY OF REMISSIONS WERE DEMONSTRATED EARLY AND WERE DURABLE1§
Patients treated with VENCLYXTO plus AZA achieved remission in a median of 1.3 months, with a number of patients responding after Cycle 2 of treatment1
MEDIAN TIME TO FIRST RESPONSE (CR OR CRi)
CR+CRi BY CYCLE 2
CR+CRi AFTER CYCLE 2II
Patients who were treated with VENCLYXTO plus AZA and achieved CR+CRi had longer remissions that lasted a median of 17.5 months vs AZA alone1
MEDIAN DURATION AND RANGE OF RESPONSE¶ (CR+CRi)
*CR=absolute neutrophil count (ANC) >1000/microlitre, platelets >100,000/microlitre, RBC transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi=CR with incomplete blood count recovery (ANC ≤1000/microlitre or platelets ≤100,000/microlitre).1,2
†CR+CRi MRD response rate is defined as the percentage of patients achieving a CR or CRi and demonstrating an MRD response of <10-3 blasts in bone marrow as determined by a standardised, central multicolour flow cytometry assay.1
‡“Hard-to-treat patient populations” refers to those patients who are ineligible for intensive chemotherapy.
§A longer median duration of response vs AZA alone.1
||The rate of CR+CRi after Cycle 2 was calculated by subtracting the rate of CR+CRi by Cycle 2 from the total CR+CRi rate.
¶Median duration of response is from Kaplan-Meier estimate and was defined as time from first response of CR or CRi to the first date of confirmed morphologic relapse, confirmed progressive disease, or death due to disease progression, whichever occurred earlier.1
VENCLYXTO PLUS AZA OFFERED MORE TRANSFUSION-FREE PERIODS THAN AZA ALONE1
Transfusion independence* was achieved in ≥60% of patients receiving VENCLYXTO plus AZA1
TRANSFUSION INDEPENDENCE RATES
| • | Of the patients who were RBC transfusion dependent at baseline and treated with VENCLYXTO plus AZA, 49% became transfusion independent |
| • | Of the patients who were platelet transfusion dependent at baseline and treated with VENCLYXTO plus AZA, 50% became transfusion independent |
*Transfusion independence was defined as a period of at least 56 consecutive days with no transfusion after the first dose of study drug and on or before the last dose of the study drug plus 30 days, or before relapse or disease progression or before the initiation of posttreatment therapy, whichever is earlier.1
†P value is from Cochran-Mantel-Haenszel test stratified by age (18-<75, ≥75) and cytogenetic (intermediate risk, poor risk) as assigned at randomisation.
AML=acute myeloid leukaemia; AZA=azacitidine; BCL-2=B-cell lymphoma 2; CI=confidence interval; CMML=chronic myelomonocytic leukaemia; CR=complete remission; CRh=complete remission with partial haematological recovery; CRi=complete remission with incomplete haematological recovery; ECOG=Eastern Cooperative Oncology Group; FLT=fms-like tyrosine kinase; HMA=hypomethylating agent; HR=hazard ratio; IDH=isocitrate dehydrogenase; MRD=minimal residual disease; MRC=myelodysplasia-related changes; NPM=nucleophosmin; NR=not reported; PO=by mouth; RBC=red blood cell; SC/IV=subcutaneous/intravenous; TP53=tumour protein p53; VEN=VENCLYXTO.
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References: 1. VENCLYXTO Summary of Product Characteristics. Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG. December 2022. 2. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971
ALL-VNCAML-220066 October 2023