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VENCLYXTO + Azacitidine (VEN+AZA)

VIALE-A study design

A PHASE 3 TRIAL COMPARING VENCLYXTO PLUS AZA vs AZA ALONE IN FIRST-LINE PATIENTS INELIGIBLE FOR INTENSIVE CHEMOTHERAPY1*

*Patients were considered ineligible for intensive chemotherapy if they were 75 years of age or older or had comorbidities that precluded the use of intensive induction chemotherapy.1

A randomised, double-blind, placebo-controlled study in newly diagnosed AML patients1

Treatment with VENCLYXTO was initiated at 100 mg on day 1, 200 mg on day 2, and the target dose of 400 mg was reached on day 3.1

AZA=azacitidine; CR=complete remission; CRi=CR with incomplete blood count recovery; MRD=minimal residual disease; PO=by mouth; SC/IV=subcutaneous/intravenous; VEN=VENCLYXTO.

Full eligibility criteria are listed in DiNardo CD et al. N Engl J Med. 2020; 383(7): 617-29 (supplementary appendix)

CHF=congestive heart failure; DLCO=diffusing capacity of the lungs for carbon monoxide; ECOG=Eastern Cooperative Oncology Group; EF=ejection fraction; FEV1=forced expiratory volume in one second; HMA=hypomethylating agent.

Baseline demographic and disease characteristics were similar between the treatment arms1

*Transfusion dependence at baseline was defined as transfusion within 8 weeks before the first dose of azacitidine–venetoclax or azacitidine–placebo or randomisation.

These bone marrow blast counts were between 20% and 29%.1

AZA=azacitidine; CMML=chronic myelomonocytic leukaemia; ECOG=Eastern Cooperative Oncology Group; MDS=myelodysplastic syndrome; RBC=red blood cell; VEN=VENCLYXTO.

  • VENCLYXTO is taken once daily with the dose increasing per the titration schedule2
  • Start VENCLYXTO and AZA on the same first day of the treatment cycle2
  • VENCLYXTO should be taken with a meal and water at approximately the same time each day
  • VENCLYXTO should not be chewed, crushed, or broken before swallowing
  • VENCLYXTO is available in 10-mg, 50-mg, and 100-mg film-coated tablets
  • Continue VENCLYXTO, in combination with AZA until disease progression or unacceptable toxicity is observed2

 

AZA=azacitidine; IV=intravenous; SC=subcutaneous.

Overall Survival

VENCLYXTO PLUS AZA SIGNIFICANTLY EXTENDED MEDIAN OVERALL SURVIVAL vs AZA ALONE IN FIRST-LINE PATIENTS INELIGIBLE FOR INTENSIVE CHEMOTHERAPY1

VENCLYXTO plus AZA demonstrated a 5.1 month increase in median overall survival vs AZA alone (14.7 months vs 9.6 months, respectively [HR=0.66; 95% CI: 0.52-0.85]; P<0.001)1*

*Hazard ratio estimate (VENCLYXTO plus AZA vs AZA alone) is based on Cox proportional hazards model stratified by age (≥18-<75, ≥75 and cytogenetics (intermediate risk, poor risk) as assigned at randomisation; P-value based on log-rank test stratified by the same factors.1

AZA=azacitidine; CI=confidence interval; HR=hazard ratio; VEN=VENCLYXTO.

*The hazard ratio for death was estimated with the unstratified Cox proportional-hazards model.1
AZA=azacitidine; CI=confidence interval; ECOG=Eastern Cooperative Oncology Group; VEN=VENCLYXTO. 

 

CR+CRi remission

A STATISTICALLY SIGNIFICANT INCREASE IN COMPOSITE COMPLETE REMISSION RATE (CR+CRi) WAS ACHIEVED WITH VENCLYXTO PLUS AZA vs AZA ALONE (66% vs 28%, P<0.001)1

VENCLYXTO plus AZA more than DOUBLED the CR+CRi rate vs AZA alone1 

Venclyxto plus AZA more than tripled the CR+CRi MRD response rate vs AZA alone1,2

*CR=absolute neutrophil count (ANC) ≥1,000/microlitre, platelets ≥100,000/microlitre, RBC transfusion independence, and bone marrow with <5% blasts; absence of circulating blasts and blast with Auer rods, and absence of extramedullary disease. CRi=ANC <1,000/microlitre or platelets <100,000/microlitre.1

CR+CRi MRD response rate was defined as the % of patients who achieved a CR or CRi and demonstrated an MRD response of <10-3 blasts in bone marrow2

AZA=azacitidine; CI=confidence interval; CR=complete remission; CRi=CR with incomplete blood count recovery; MRD=minimal residual disease; RBC=red blood cell; VEN=VENCLYXTO.


Transfusion independence

VENCLYXTO PLUS AZA OFFERED GREATER TRANSFUSION INDEPENDENCE vs AZA ALONE1

Significantly more patients who received VENCLYXTO plus AZA achieved transfusion independence vs AZA alone1

 

*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 post-treatment therapy, whichever is earlier.1,2

AZA=azacitidine; CI=confidence interval; RBC=red blood cell; VEN=VENCLYXTO.


Safety profile

VENCLYXTO PLUS AZA DEMONSTRATED A GENERALLY MANAGEABLE ADVERSE EVENT PROFILE1

For a full list of adverse events please see the SmPC.

*Adverse events of grade 3 or higher that were reported in at least 10% of patients in either treatment group are listed.1

Adverse events reported in at least 20% of patients in either treatment group are listed.1

Serious adverse events that were reported in at least 5% of patients in either treatment group are listed.1

AE=adverse event; AZA=azacitidine; TLS=tumour lysis syndrome; VEN=VENCLYXTO; WBC=white blood cell count.


References

  1. DiNardo CD et al. N Engl J Med. 2020; 383(7): 617-29. 
  2. VENCLYXTO Summary of Product Characteristics.

 

Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.

Adverse events should also be reported to AbbVie on GBPV@abbvie.com

UK-VNCAML-220115. Date of preparation: April 2022.