Dasatinib may be considered a new standard of care for pediatric patients with CML-CP

Madrid, June 2017 -Findings from a large prospective trial with pediatric patients¹ suggest that dasatinib provides benefits to children and adolescents in CML-CP who are resistant /intolerant to imatinib.

CML represents less than 3% of all leukemias in children worldwide, but more aggressive disease characteristics have been observed in this patient population.

Currently imatinib is the only approved tyrosine kinase inhibitor in children with CML and no approved therapies are available for children resistant or intolerant to imatinib. "There is an unmet need for safe and effective treatment options for children and adolescents who are resistant or intolerant to imatinib and also for alternative treatment formulations", Dr C. Zwaan opened his presentation at the 22th meeting of the European Hematology Association (EHA) in Madrid.

According to Dr. Zwaan, dasatinib has already shown to be effective in adults with newly diagnosed CML-CP, as well as those resistant/intolerant to imatinib however, "there is almost no published data available in children who are resistant or intolerant to imatinib".

Zwaan presented data from a Phase II open-label, randomized, prospective study conducted in 18 countries. In this large, ongoing prospective trial of pediatric patients with CML-CP, dasatinib was found to be safe and effective as first, or second-line therapy.

Patients aged <18 years were recruited into three separate cohorts: (1) IM-resistant/intolerant CML-CP treated with dasatinib 60 mg/m2 QD, (2) IM-resistant/intolerant CML-AP/BP or Ph+ ALL, and (3) newly diagnosed CML-CP treated with dasatinib 60 mg/m2 or dasatinib 72 mg/m2 powder for oral suspension QD for ≥1 year. Within the imatinib resistant/intolerant group of 29 patients, 25 patients were resistant, 2 intolerant and 2 undetermined.

The primary objectives were MCyR for imatinib resistant/intolerant CML-CP at any time with more than 30% MCyR as the protocol-defined rate of clinical interest and CCyR for newly diagnosed CML-CP at any time with more than 55% CCyR as the protocol-defined rate of clinical interest.

The cumulative rate of MCyR >30% was reached as early as 3 months for IM-resistant/intolerant CML-CP, and a cumulative rate of CCyR >55% was reached as early as 6 months for newly diagnosed CML-CP. Cytogenetic and molecular response continued to increase over time in each cohort. "Early and durable responses to dasatinib were observed, which met the study objectives for both cohorts”, Zwaan summed up the efficacy study results.

The safety profile of dasatinib was comparable to previous reports in adults treated with dasatinib except that no cases of pleural/pericardial effusion or pulmonary arterial hypertension were observed. 

Additional advantages include; once-daily dosing and administration with, or without food.

In conclusion, according to Zwaan, this is the largest prospective trial with pediatric patients and dasatinib was found to be a safe and effective treatment for pediatric patients in chronic-phase CML. The safety profile was slightly favourable to adult data with respect to the absence of effusions. “Further investigation is needed to determine whether the reasons for this slightly better safety profile in pediatric patients are due to a better immune system or any other reason”, Zwaan concluded at the end of his presentation.

1. Dasatinib in children and adolescents with chronic myeloid leukemia in chronic phase (CML-CP) from a phase 2 trial, abstract presented by CM Zwaan during the 22nd Congress of the European Hematology Association (EHA), June 22-25, 2017 in Madrid, Spain.

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