Does a higher dose of dasatinib increase chances of patients with Philadelphia chromosome positive acute lymphoblastic leukemia at risk for CNS relapse?

The study aimed to investigate the ability of dasatinib (Sprycel) to penetrate the brain in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) at risk for central nervous system (CNS; brain and spinal cord) relapse.  

This study concluded that a dose of 140mg per day of dasatinib is recommended in these patients to penetrate the CNS. 

Ph+ ALL is an aggressive type of ALL. Up to 10% of patients have CNS involvement at diagnosis and another 15% can have relapse of ALL in the CNS. Treatments for ALL include targeted therapies. Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) with higher CNS penetration compared to ibrutinib (Imbruvica) and nilotinib (Tasigna).  

In order to penetrate the CNS, the substance must cross the blood-brain barrier (BBB). The BBB is a boundary between blood and the brain. It allows certain substances such as nutrients to cross into the brain while keeping substances like toxins and pathogens out of the brain. There are a few drugs that can cross the BBB. However, there is limited data available about the dosage and CNS penetration of dasatinib. 

This study involved 30 patients with Ph+ ALL. All patients were treated with dasatinib 100mg daily. The dose of dasatinib was increased to 140mg daily (2 70mg doses per day) in 5 patients due to a poor response. Plasma and cerebrospinal fluid (CSF) samples were collected from these patients to test the penetration of the drug.

Orally administered dasatinib 100 mg once daily was well absorbed but penetrated poorly into the CSF. All 5 patients who were given 140 mg dasatinib had detectable dasatinib levels in the CSF. No patient needed to stop treatment during the study.

This study concluded that in patients with Ph+ CLL, the use of a higher dosage of dasatinib (140mg per day) may be recommended for patients at high risk of CNS relapse.

This study had a small number of participants and was not designed to test for the effectiveness of dasatinib for patients with CNS relapse risk. Further studies are needed to test the dose of 140mg dasatinib in these patients.