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 certain 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 .
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 lowdose 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 .
Adverse Reactions : Most common adverse reactions associated with DAURISMO ( incidence ≥20 %) were anemia ( 43 %), fatigue ( 36 %), hemorrhage ( 36 %), febrile neutropenia ( 31 %), musculoskeletal pain ( 30 %), edema ( 30 %), thrombocytopenia ( 30 %), nausea ( 29 %), dyspnea ( 23 %), decreased appetite ( 21 %), dysgeusia ( 21 %), mucositis ( 21 %), constipation ( 20 %), and rash ( 20 %).