Dasatinib safe, effective for pediatric chronic myeloid leukemia in chronic phase
Dasatinib appeared safe and effective for the treatment of children with chronic myeloid leukemia in chronic phase, according to findings published in Journal of Clinical Oncology.
“The development of safe and effective therapies for pediatric CML is critical for the successful treatment of this patient population,” Lia Gore, MD, associate professor in the division of medical oncology at University of Colorado Anschutz Medical Campus, and colleagues wrote. “Until recently, the BCR-ABL1-target tyrosine kinase inhibitor imatinib was the only TKI approved for frontline treatment of pediatric patients with CML in chronic phase; however, 25% to 29% discontinue as a result of poor response or toxicity. ... Dasatinib [Sprycel; Bristol-Myers Squibb, Ostuka] is a second-generation TKI that is now approved in tablet formulation for the treatment of pediatric patients with CML in chronic phase.”
The researchers performed a phase 2, open-label nonrandomized prospective trial of 130 patients aged younger than 18 years with CML in chronic phase.
The study consisted of three cohorts: patients with imatinib-resistant or -intolerant disease (n = 29), patients with imatinib-resistant or -intolerant disease in accelerated/blast phase or Ph+ALL (n = 17), and patients newly diagnosed with CML in chronic phase (n = 84). Newly diagnosed patients were either received dasatinib tablets (n = 51) or powder for oral suspension for at least 12 months (n = 33).
Researchers deemed major cytogenetic response greater than 30% for imatinib-resistant/intolerant patients and complete cytogenetic response greater than 55% for newly diagnosed patients of clinical interest.
Fourteen patients (48%) with imatinib resistance or intolerance and 61 newly diagnosed patients (73%) remained on treatment at the time of analysis.
The imatinib-resistant/intolerant group achieved major cytogenic response of more than 30% by 3 months. The newly diagnosed group achieved complete cytogenetic response of more than 55% by the 6-month mark.
By 12 months, the imatinib-resistant/intolerant group had a complete cytogenetic response rate of 76% and a major molecular response rate of 41%. The newly diagnosed group demonstrated a complete cytogenetic response rate of 92% and major molecular response rate of 52%.
At 48 months, 78% of the imatinib-resistant/intolerant group achieved PFS, compared with 93% of the newly diagnosed group.
Researchers observed no instances of dasatinib-related pleural or pericardial effusion, pulmonary edema or pulmonary arterial hypertension. Four percent of patients experienced bone growth and development events.
“Overall, dasatinib treatment produced early, deep and durable responses of clinical importance in this largest prospective trial of pediatric patients with CML in chronic phase to date,” the researchers wrote.
“These results support dasatinib as a safe and effective first- or second-line option for the treatment of pediatric CML in chronic phase,” they added. – by Andy Polhamus
Disclosures: Gore reports stock or other ownership in Amgen, Celgene, Clovis Oncology and Sanofi; an immediate family member with stock or other ownership in ARIAD and Ignyta; honoraria from Amgen, Bristol-Myers Squibb and Novartis; consultant/advisory roles with Amgen, Celgene, Medscape, Novartis, ProEd Communications and Roche; patents for diagnostic discovery and treatment response methodology tools in the use of magnetic resonance spectroscopy for leukemia; and travel and accommodations expenses from Amgen, Bristol-Myers Squibb, Novartis and Roche. Please see the full study for a list of all other authors’ relevant financial disclosures.