Dasatinib for Pediatric Chronic Myeloid Leukemia in Chronic Phase
As reported in the Journal of Clinical Oncology by Gore et al, a phase II trial has shown high response rates with dasatinib treatment in pediatric patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP).
Findings in the trial supported the November 2017 approval of dasatinib in this setting.
Study Details
The trial included patients aged < 18 years in 3 cohorts of patients with Ph+ leukemia: (1) imatinib-resistant/intolerant CML-CP (n = 29), (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension (n = 84). Major cytogenetic response in > 30% of imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) in > 55% of newly diagnosed patients were outcomes of interest.
Responses
Among the 113 patients with CML-CP, 14 (48%) of 29 who were imatinib-resistant/intolerant and 61 (73%) of 84 who were newly diagnosed remained on treatment at time of analysis. A major cytogenetic response rate > 30% was reached by 3 months in the imatinib-resistant/intolerant group and a complete cytogenetic response rate > 55% was reached by 6 months in the newly diagnosed CML-CP group.
At 12 months, the complete cytogenetic response and major molecular response rates were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in the newly diagnosed CML-CP group. The progression-free survival rate at 48 months was 78% in the imatinib-resistant/intolerant group and 93% in the newly diagnosed CML-CP group.
Toxicity
No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Overall, bone growth and development events were reported in 4% of patients. Among patients with imatinib-resistant/intolerant CML-CP and newly diagnosed patients, any-grade myalgia and arthralgia occurred in 17% and 10%, and any-grade fatigue occurred in 14% and 11%. Dasatinib-related serious adverse events occurred in 17% and 10%.
The investigators concluded, “In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.”
The study was supported by Bristol-Myers Squibb.
Lia Gore, MD, of the University of Colorado Anschutz Medical Campus, Children’s Hospital Colorado, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
