Responses for CR and CRh were reached at different times throughout treatment; management of Grade 4 neutropenia or thrombocytopenia differs before and after remission is achieved 1

  • In VIALE-A, bone marrow assessment was conducted following Cycle 1 treatment. Once bone marrow assessment confirmed a remission,* VENCLEXTA (venetoclax tablets) or placebo was interrupted up to 14 days or until ANC ≥500/microliter and platelet count ≥50 x 103/microliter
    • For patients with resistant disease after the end of Cycle 1, a bone marrow assessment was performed after Cycle 2 or 3 and as clinically indicated
Select secondary endpoints: CR, CR+CRh 1,3
Endpoint  VEN+AZA (N=286) PBO+AZA (N=145)
CR, n (%), (95% CI) 105 (37), (31, 43) 26 (18), (12, 25)
P value <0.001
Median DOCR (months), (95% CI) 18 (15.3, –) 13.4 (8.7, 17.6)
CR+CRh, n (%), (95% CI) 185 (65), (59, 70) 33 (23), (16, 30)
P value <0.001
Median DOCR+CRh (months), (95% CI) 17.8 (15.3, –) 13.9 (10.4, 15.7)

The median time to first response of CR or CRh was 1.0 months (range: 0.6-14.3 months) with VEN+AZA treatment; some patients achieved CR or CRh in later cycles 1,4

Secondary endpoint: CR+CRh by initiation of Cycle 2 3

  • 40% (n=114/286) with VEN+AZA (95% CI: [34, 46]; P<0.001)

In an exploratory post hoc analysis of CR+CRh in the VEN+AZA ITT population 4:

  • 47% (134/286) achieved CR+CRh by the beginning of Cycle 3
  • 50% (143/286) achieved CR+CRh by the beginning of Cycle 4

Management: Recommendations for cytopenias and non-hematologic adverse reactions 1

  • Monitor blood counts frequently through resolution of cytopenias. Dose modification and interruptions for cytopenias are dependent on remission status. See recommendations below

In VIALE-A:

  • Exploratory post hoc analysis: 75% of patients in remission (139/186) had at least 1 pause in dosing lasting 7+ days 4
  • In the VEN+AZA arm, among patients who achieved bone marrow clearance of leukemia, 53% (114/216)II underwent dose interruptions for ANC <500/microliter 1,7
  • Once bone marrow assessment confirmed a remission, defined as less than 5% leukemia blasts with cytopenia, VENCLEXTA or placebo was interrupted up to 14 days or until ANC ≥500/microliter and platelet count ≥50 × 103/microliter 1

*Defined as less than 5% leukemia blasts with cytopenia.
Recommend bone marrow evaluation.
Remission is defined as achieving a CR or CRh.
§Dose may vary based on drug-drug interactions or severe hepatic impairment.
IIOf patients who achieved a morphologic leukemia-free state of response or better. 7

ITT=intent to treat; VEN=VENCLEXTA; AZA=azacitidine; PBO=placebo; ANC=absolute neutrophil count.

Complete remission (CR) was defined as ANC >1,000/microliter, platelets >100,000/microliter, red blood cell transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. 1

Complete remission with partial hematologic recovery (CRh) was defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter). 1