The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for dasatinib (Sprycel).
The CHMP’s recommendation is to approve dasatinib in combination with chemotherapy to treat pediatric patients with newly diagnosed, Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of a CHMP recommendation.
Dasatinib is already EC-approved to treat:
- Adults with newly diagnosed, Ph+ chronic myelogenous leukemia (CML) in the chronic phase
- Adults with chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib
- Adults with Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy
- Pediatric patients with newly diagnosed, Ph+ CML in chronic phase
- Pediatric patients with Ph+ CML in chronic phase that is resistant or intolerant to prior therapy including imatinib.
Phase 2 trial
The CHMP’s recommendation to approve dasatinib in pediatric patients with newly diagnosed, Ph+ ALL is based on data from a phase 2 trial (NCT01460160). In this trial, researchers are evaluating dasatinib in combination with a chemotherapy regimen modeled on a Berlin-Frankfurt-Munster high-risk backbone.
Results from the trial were presented at the 2017 ASH Annual Meeting.
At that time, 106 patients had been treated. They received continuous daily dasatinib (60 mg/m2) beginning at day 15 of induction chemotherapy. All treated patients achieved complete remission.
Patients who had evidence of minimal residual disease (MRD) ≥ 0.05% at the end of the first block of treatment (day 78) and those with MRD 0.005% to 0.05% who remained MRD-positive at any detectable level after three additional high-risk chemotherapy blocks were eligible for hematopoietic stem cell transplant (HSCT) in first remission.
Nineteen patients met these criteria, and 15 (14.2%) received HSCT. The remaining 85.8% of patients received dasatinib plus chemotherapy for two years.
The 3-year event-free survival rate was 65.5%, and the 3-year overall survival rate was 91.5%.
Two patients discontinued dasatinib due to toxicity—one due to allergy and one due to prolonged thrombocytopenia.
Grade 3/4 adverse events attributed to dasatinib included elevated alanine aminotransferase (21.7%), elevated aspartate transaminase (10.4%), pleural effusion (3.8%), edema (2.8%), hemorrhage (5.7%), and cardiac failure (0.8%).
Five patients died while receiving chemotherapy (three from sepsis, one due to pneumonia, and one of an unknown cause). Two deaths were HSCT-related.
This trial was sponsored by Bristol-Myers Squibb.