Written in Blood
HL), an Eastern Cooperative Oncology
Group performance status score of ≤3, and
declined or were ineligible for standard front-
line chemotherapy. Those with symptom-
atic neurologic disease that impaired daily
activities or that required medications were
excluded, as were those with kidney disease
requiring ongoing dialysis.
Patients were assigned to receive either:
• BV 1.8 mg/kg plus dacarbazine
376 mg/m 2 for up to 12 cycles
(n=22; median age = 69 years; range
= 62-88 years)
• BV 1.8 mg/kg plus bendamustine
90 mg/m 2 for up to 6 cycles (n=20;
median age = 75 years; range = 63-86
years)
Subsequent BV therapy was allowed in
each arm.
Nearly half of patients in each cohort (11
[50%] in the BV plus dacarbazine cohort
and 9 [45%] in the BV plus bendamustine
cohort) reported having three or more co-
morbidities or one or more comorbidity that
significantly interfered with their life. Most
(16 [72%] in the BV plus dacarbazine cohort
and 15 [75%] in the BV plus bendamustine
cohort) had stage III/IV disease.
For the 21 evaluable patients treated
with BV plus dacarbazine and the 17
Other notable adverse drug reactions that occurred in less than 10% of
patients treated with VYXEOS during induction or consolidation included:
• Ear and labyrinth disorders: Deafness, Deafness unilateral
• Eye Disorders: Eye conjunctivitis, Dry eye, Eye edema, Eye swelling,
Eye irritation, Eye pain, Ocular discomfort, Ocular hyperemia,
Periorbital edema, Scleral hyperemia
• Gastrointestinal disorders: Dyspepsia
• Psychiatric disorders: Hallucinations
• Respiratory, thoracic and mediastinal disorders: Pneumonitis
Laboratory Abnormalities
All patients developed severe neutropenia, thrombocytopenia, and anemia.
See Table 3 for the incidences of Grade 3 thrombocytopenia and Grade 4
neutropenia that were prolonged in the absence of active leukemia.
Table 3: Prolonged Cytopenias for Patients in Study 1
Induction 1
VYXEOS
7+3
N=58
N=34
n (%)
n (%)
Prolonged
thrombocytopenia a
Prolonged
neutropenia a
Consolidation 1 b
VYXEOS
5+2
N=48
N=32
n (%)
n (%)
16 (28) 4 (12) 12 (25) 5 (16)
10 (17) 1 (3) 5 (10) 1 (3)
Platelets <50 Gi/L or neutrophils <0.5 Gi/L lasting past cycle day 42
in the absence of active leukemia.
b
Patients receiving at least 1 consolidation.
a
Grade 3-4 chemistry abnormalities occurring in greater than 5%
of VYXEOS treated patients in Study 1 are presented in Table 4.
Table 4: Grade 3-4 a Chemistry Abnormalities ≥5% of VYXEOS
Treated Patients in Study 1
Induction
VYXEOS
7+3
N=153
N=151
n (%)
n (%)
Chemistry Abnormalities
Hyponatremia
21 (14)
20 (13)
Hypokalemia
14 (9)
19 (13)
Hypoalbuminemia
11 (7)
19 (13)
Hyperbilirubinemia
9 (6)
6 (4)
Alanine
7 (5)
8 (5)
aminotransferase
Consolidation
VYXEOS
5+2
N=49
N=32
n (%)
n (%)
3 (6)
3 (6)
1 (2)
1 (2) 0
2 (6)
4 (13)
1 (3)
0 1 (3)
Graded using NCI CTCAE version 3.0.
a
DRUG INTERACTIONS
Cardiotoxic Agents
Concomitant use of cardiotoxic agents may increase the risk of
cardiotoxicity. Assess cardiac function more frequently when VYXEOS
is coadministered with cardiotoxic agents [see Warnings and Precautions].
Hepatotoxic Agents
Concomitant use with hepatotoxic agents may impair liver function
and increase the toxicity of VYXEOS. Monitor hepatic function more
frequently when VYXEOS is coadministered with hepatotoxic agents.
evaluable patients treated with BV plus
bendamustine, the ORR (primary end-
point) was 100 percent in both cohorts.
“Despite the advanced age … and signifi-
cant comorbidity burden of these patients,
the majority achieved a CR,” the authors
wrote:
• BV plus dacarbazine: 13 CRs (62%)
and 8 partial responses (PR; 38%)
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Based on anecdotal data of cytarabine in pregnant women and results
of studies of daunorubicin and cytarabine in animals, VYXEOS can
cause embryo-fetal harm when administered to a pregnant woman.
There are no adequate and well-controlled studies of VYXEOS,
daunorubicin, or cytarabine in pregnant women. Daunorubicin and
cytarabine are reproductive and developmental toxicants in multiple
species (mice, rats, and/or dogs), starting at a dose that was approximately
0.02 times the exposure in patients at the recommended human dose
on a mg/m 2 basis [see Animal Data]. Patients should be advised to avoid
becoming pregnant while taking VYXEOS. If this drug is used during
pregnancy or if the patient becomes pregnant while taking this drug,
apprise the patient of the potential harm to a fetus.
The estimated background risk of major birth defects and miscarriage
for the indicated population is unknown. Adverse outcomes in pregnancy
occur regardless of the health of the mother or the use of medications. In
the U.S. general population, the estimated background risks of major birth
defects and miscarriage in clinically recognized pregnancies are 2 to 4%
and 15 to 20%, respectively.
Data
Human Data
Cytarabine can cause fetal harm if a pregnant woman is exposed to
the drug. Four anecdotal cases of major limb malformations have been
reported in infants after their mothers received intravenous cytarabine,
alone or in combination with other agents, during the first trimester.
Animal Data
A liposomal formulation of daunorubicin was administered to rats on
gestation days 6 through 15 at 0.3, 1.0, or 2.0 mg/kg/day (about 0.04, 0.14,
or 0.27 the recommended human dose on a mg/m 2 basis) and produced
severe maternal toxicity and embryolethality at 2.0 mg/kg/day and
was embryotoxic and caused fetal malformations (anophthalmia,
microphthalmia, incomplete ossification) at 0.3 mg/kg/day. Embryotoxicity
was characterized by increased embryo-fetal deaths, reduced numbers
of litters, and reduced litter sizes.
Cytarabine was teratogenic in mice (cleft palate, phocomelia, deformed
appendages, skeletal abnormalities) when doses ≥2 mg/kg/day were
administered IP during the period of organogenesis (about 0.06 times
the recommended human dose on a mg/m 2 basis), and in rats
(deformed appendages) when 20 mg/kg was administered as a single
IP dose on day 12 of gestation (about 1.2 times the recommended human
dose on a mg/m 2 basis). Single IP doses of 50 mg/kg in rats (about
3 times the recommended human dose on a mg/m 2 basis) on day 14
of gestation redu