ASH Clinical News ACN_5.12_FULL ISSUE digital | Page 2

Adding DAURISMO to low-dose cytarabine (LDAC) significantly extended overall survival (OS)
in adults with newly diagnosed AML who were aged ≥75 years or had other comorbidities
that precluded use of intensive induction chemotherapy 1,2
Study description: BRIGHT AML 1003 was a randomized (2:1), open-label, multicenter trial in 115 patients with newly
diagnosed AML not eligible for intensive chemotherapy who met at least one of the following criteria: (a) aged ≥75
years, (b) severe cardiac disease, (c) baseline ECOG performance status of 2, or (d) baseline serum creatinine
>1.3 mg/dL. Patients received either 100 mg of DAURISMO oral once daily, given continuously in combination with
LDAC, or LDAC alone. OS was the primary endpoint. 1
INCLUDED IN THE
NCCN GUIDELINES ®
Glasdegib (DAURISMO) in combination with low-dose cytarabine is included as a category 2A treatment
option in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for adults with newly
diagnosed AML who are not candidates for or decline intensive induction therapy. 3
AML=acute myeloid leukemia; AR=adverse reaction; CI=confidence interval; ECOG=Eastern Cooperative Oncology Group;
HR=hazard ratio; NCCN=National Comprehensive Cancer Network.
INDICATION
DAURISMO is a hedgehog pathway inhibitor indicated, in
combination with low-dose cytarabine, for the treatment
of newly diagnosed acute myeloid leukemia (AML) in adult
patients who are ≥75 years old or who have comorbidities
that preclude use of intensive induction chemotherapy.
Limitation of Use: DAURISMO has not been studied in
patients with the comorbidities of severe renal impairment
or moderate-to-severe hepatic impairment.
IMPORTANT SAFETY INFORMATION
WARNING: EMBRYO-FETAL TOXICITY: DAURISMO
can cause embryo-fetal death or severe birth defects
when administered to a pregnant woman. DAURISMO is
embryotoxic, fetotoxic, and teratogenic in animals. Conduct
pregnancy testing in females of reproductive potential
prior to initiation of DAURISMO treatment. Advise females
of reproductive potential to use effective contraception
during treatment with DAURISMO and for at least 30 days
after the last dose. Advise males of the potential risk of
DAURISMO exposure through semen and to use condoms
with a pregnant partner or a female partner of reproductive
potential during treatment with DAURISMO and for at least
30 days after the last dose to avoid potential drug exposure.
Blood Donation: Advise patients not to donate blood or blood
products while taking DAURISMO and for at least 30 days after
the last dose, because their blood or blood products might be
given to a female of reproductive potential.
QTc Interval Prolongation: Patients treated with DAURISMO
can develop QTc prolongation and ventricular arrhythmias,
including ventricular fibrillation and ventricular tachycardia.
Of the 98 evaluable patients treated with DAURISMO 100
mg in combination with low-dose cytarabine in the clinical
trial, 5% were found to have a QTc interval greater than 500
ms and 4% of patients had an increase from baseline QTc
greater than 60 ms. The clinical trial excluded patients with
baseline QTc of greater than 470 ms or with a history of long
QT syndrome or uncontrolled cardiovascular disease. Monitor
electrocardiograms (ECGs) and electrolytes. Concomitant
use of DAURISMO with drugs known to prolong the QTc
interval and CYP3A4 inhibitors may increase the risk of QTc
interval prolongation. In patients with congenital long QT
syndrome, congestive heart failure, electrolyte abnormalities,
or those who are taking medications known to prolong the
QTc interval, more frequent ECG monitoring is recommended.
Interrupt DAURISMO if QTc interval is >500 ms and discontinue
permanently for patients who develop QTc interval prolongation
with signs or symptoms of life-threatening arrhythmia.