A tolerable, manageable, and predictable safety profile 1

No additional warnings or precautions were observed in the AML trials for VENCLEXTA (venetoclax tablets). The safety profile of VEN+AZA was consistent with the known side effect profile of both agents.

Adverse reactions (≥10%) in patients with AML who received VEN+AZA with a difference between arms of ≥5% for all grades or ≥2% for Grade 3 or 4 reactions compared with PBO+AZA 1*

Adverse reaction by body system
  VEN+AZA
(N=283)
PBO+AZA
(N=144)
Body system Adverse reaction All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Gastrointestinal disorders  Nausea 44 2 35 <1
Diarrhea 43 5 33 3
Vomiting 30 2 23 <1
Stomatitis 18 1 13 0
Abdominal pain 18 <1 13 0
Blood and lymphatic system disorders Febrile neutropenia 42 42 19 19
Musculoskeletal and connective tissue disorders Musculoskeletal pain 36 2 28 1
General disorders and administration site conditions Fatigue 31 6 23 2
Edema 27 <1 19 0
Vascular disorders Hemorrhage 27 7 24 3
Hypotension 12 5 8 3
Metabolism and nutrition disorders Decreased appetite 25 4 17 <1
Skin and subcutaneous tissue disorders Rash 25 1 15 0
Infections and infestations   Sepsis
(excluding fungal)
22 22 16 14
Urinary tract infection 16 6 9 6
Respiratory, thoracic, and mediastinal disorders Dyspnea 18 4 10 2
Nervous system disorders Dizziness 17 <1 8 <1

*Patients who received at least one dose of either treatment.
Includes multiple adverse reaction terms.

Hematologic laboratory abnormalities 1

New or worsening Grade 3 or 4 hematologic laboratory abnormalities in VIALE-A with a difference between arms of ≥2% for VEN+AZA vs PBO+AZA, respectively:

  • Neutrophils decreased 98% vs 81%
  • Platelets decreased 88% vs 80%
  • Lymphocytes decreased 71% vs 39%
  • Hemoglobin decreased 57% vs 52%

Duration of exposure and occurrence of adverse reactions

Rate of serious adverse reactions
  VEN+AZA (N=283) 1 PBO+AZA (N=144) 3,5
  (%) occurrence

Most frequent

adverse reaction(s)

(%) occurrence

Most frequent

adverse reaction(s)

Serious ARs 83 ≥5%: febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%), hemorrhage (6%)
73 ≥5%: pneumonia (22%), febrile neutropenia (10%), sepsis (8%)
Fatal ARs 23

>2%: pneumonia (4%), sepsis (excluding fungal; 3%), hemorrhage (2%)

20 ≥2%: sepsis (4%), pneumonia (2%)
Discontinuation, reduction, and interruption rates of VEN or PBO
  VEN VEN+AZA PBO PBO+AZA
ARs leading to permanent drug  discontinuation 24 >2%: sepsis (excluding fungal; 3%), pneumonia (2%) 20 ≥2%: sepsis (4%), pneumonia (3%), thrombocytopenia (2%), malignant neoplasm progression (2%)
Most frequent AR leading to dose reductions 3 5 pneumonia (0.7%) 4 pneumonia (1%)
ARs leading to dose interruptions 72 ≥5%: febrile neutropenia (20%), neutropenia (20%), pneumonia (14%), sepsis (excluding fungal; 11%), thrombocytopenia (10%) 57 ≥5%: pneumonia (13%), neutropenia (10%)
• In the VEN+AZA arm, among patients who achieved bone marrow clearance of leukemia, 53% (114/216) 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 or platelet count ≥50 x 103/microliter 1
• Azacitidine was resumed on the same day as VENCLEXTA or placebo following interruption 1
• Azacitidine dose reduction was implemented in the clinical trial for management of hematologic toxicity 1

Of patients who achieved a morphologic leukemia-free state of response or better. 7

AR=adverse reaction; VEN=VENCLEXTA; AZA=azacitidine; PBO=placebo; ANC=absolute neutrophil count.

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