The first dual-drug liposomal encapsulation of daunorubicin and cytarabine shown to...
Deliver superior overall survival vs 7+3
a
to adults with newly-diagnosed t-AML or AML-MRC 1
VYXEOS improved overall survival compared to 7+3 in a Phase 3 trial 1
• Median survival of 9.6 months for VYXEOS vs 5.9 months for 7+3 (P=0.005), HR=0.69 (0.52, 0.90)
Study Design 1
The Phase 3 study was a randomized, multicenter, open-label, active-controlled superiority study of VYXEOS versus cytarabine and
daunorubicin (7+3) in patients 60 to 75 years of age with newly-diagnosed t-AML or AML-MRC. There were 153 patients randomized
to VYXEOS and 156 patients randomized to the 7+3 arm. Twenty percent had t-AML, 54% had AML with an antecedent hematological
disorder, and 25% had de novo AML with MDS-related cytogenetic abnormalities. Efficacy was established on the basis of overall
survival from the date of randomization to death from any cause.
VYXEOS 44 mg/100 mg per m 2 (daunorubicin/cytarabine) was given intravenously on Days 1, 3, and 5 for first induction and on Days 1 and 3
for those needing a second induction. For consolidation, the VYXEOS dose was 29 mg/65 mg per m 2 (daunorubicin/cytarabine) on
Days 1 and 3. In the 7+3 arm, first induction was cytarabine 100 mg/m 2 /day on Days 1-7 by continuous infusion + daunorubicin
60 mg/m 2 /day on Days 1-3. For second induction and consolidation, cytarabine was dosed on Days 1-5 and daunorubicin on Days 1 and 2.
Patients could receive up to 2 cycles of induction and 2 cycles of consolidation in each arm. Subsequent induction was recommended
for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts.
INDICATION
VYXEOS (daunorubicin and cytarabine) liposome for
injection 44 mg/100 mg is indicated for the treatment of
adults with newly-diagnosed therapy-related acute myeloid
leukemia (t-AML) or AML with myelodysplasia-related
changes (AML-MRC).
IMPORTANT SAFETY INFORMATION
WARNING: DO NOT INTERCHANGE
WITH OTHER DAUNORUBICIN AND/OR
CYTARABINE-CONTAINING PRODUCTS
VYXEOS has different dosage recommendations
than daunorubicin hydrochloride injection, cytarabine
injection, daunorubicin citrate liposome injection, and
cytarabine liposome injection. Verify drug name and
dose prior to preparation and administration to avoid
dosing errors.
Contraindications
VYXEOS is contraindicated in patients with a history
of serious hypersensitivity reactions to cytarabine,
daunorubicin, or any component of the formulation.
Warnings and Precautions
Hemorrhage
Serious or fatal hemorrhage events, including fatal CNS
hemorrhages, associated with prolonged thrombocytopenia,
have occurred with VYXEOS. The overall incidence (grade 1-5)
of hemorrhagic events was 74% in the VYXEOS arm and 56%
in the control arm. The most frequently reported hemorrhagic
event was epistaxis (36% in VYXEOS arm and 18%
in control arm). Grade 3 or greater events occurred in
12% of VYXEOS-treated patients and in 8% of patients
in the control arm. Fatal treatment-emergent CNS
hemorrhage not in the setting of progressive disease
occurred in 2% of patients in the VYXEOS arm and
in 0.7% of patients in the control arm. Monitor blood
counts regularly and administer platelet transfusion
support as required.
Cardiotoxicity
VYXEOS contains daunorubicin, which has a known risk
of cardiotoxicity. This risk may be increased in patients
with prior anthracycline therapy, preexisting cardiac
disease, previous radiotherapy to the mediastinum, or
concomitant use of cardiotoxic drugs. Assess cardiac
function prior to VYXEOS treatment and repeat prior
to consolidation and as clinically required. Discontinue
VYXEOS in patients with impaired cardiac function
unless the benefit of initiating or continuing treatment
outweighs the risk. VYXEOS is not recommended in
patients with cardiac function that is less than normal.
Total cumulative doses of non-liposomal daunorubicin
greater than 550 mg/m 2 have been associated with
an increased incidence of drug-induced congestive
heart failure. The tolerable limit appears lower
(400 mg/m 2 ) in patients who received radiation therapy
to the mediastinum. Calculate the lifetime cumulative
anthracycline exposure prior to each cycle of VYXEOS.
VYXEOS is not recommended in patients whose lifetime
anthracycline exposure has reached the maximum
cumulative limit.