The U.S. Food and Drug Administration (FDA) has approved a second pediatric indication for dasatinib (Sprycel®).
The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients age 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Dasatinib is also FDA-approved for use in children age 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).
In adults, dasatinib is FDA-approved to treat:
- Newly diagnosed, Ph+, chronic phase CML
- Chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib
- Ph+ ALL with resistance or intolerance to prior therapy.
The FDA’s approval of dasatinib in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).
In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 chemotherapy protocol in patients (ages 1 to 17) with newly diagnosed, B-cell precursor, Ph+ ALL.
There were 78 patients evaluated for efficacy in cohort 1. They had a median age of 10.4 years (range, 2.6 to 17.9 years). They received dasatinib at a daily dose of 60 mg/m2 for up to 24 months.
Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.
The 3-year event-free survival rate in the 78 patients was 64.1%.
There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months (range, 2 to 27 months).
The most common adverse events (AEs) in these patients were mucositis (93%), febrile neutropenia (86%), pyrexia (85%), diarrhea (84%), nausea (84%), vomiting (83%), musculoskeletal pain (83%), abdominal pain (78%), cough (78%), headache (77%), rash (68%), fatigue (59%), and constipation (57%).
Eight (10%) patients had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.
Three patients (4%) had fatal AEs, all infections.
This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.