Dasatinib effective and safe for children with chronic myeloid leukaemia in chronic phase
Recent results of a phase II trial showed favourable responses to dasatinib in patients with imatinib-resistant/intolerant or newly diagnosed chronic myeloid leukaemia in chronic phase (CML-CP), according to findings presented at the 22nd Congress of European Hematology Association (EHA 2017) held in Madrid, Spain.
In the phase II, open label, nonrandomized prospective trial of 130 patients with imatinib-resistant/intolerant or newly diagnosed CML-CP, treatment with dasatinib resulted in a major cytogenetic response of more than 30 percent in 3 months among patients with imatinib-resistant/intolerant CML-CP, and a cumulative rate of complete cytogenetic response of more than 55 percent in 6 months among patients with newly diagnosed CML-CP. [EHA 2017, abstract S422]
Estimated progression-free survival (PFS) rate at 48 months was 78 percent for imatinib-resistant/intolerant CML-CP and 93 percent for newly diagnosed CML-CP.
The imatinib-resistant/intolerant group received dasatinib tablets at a dosage of 60 mg/m2 once per day, whereas the newly diagnosed group was given the same dose or the liquid formulation at 72 mg/m2 once per day.
The adverse effects were minor and similar to the ones reported in adults, occurring in about 10 percent of the patients. These events included nausea, vomiting, myalgia, arthralgia and fatigue.
Apart from these adverse events, bone growth and development were not affected and there were no cases of epiphyses delayed fusion or osteopenia reported in the study.
“This is the largest ongoing, prospective trial of paediatric patients with CML-CP and we found that dasatinib was safe and effective as first- or second-line therapy in children,” said author Dr Michael Zwaan from the Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands.
“These data suggest that dasatinib may be considered a new standard of care for paediatric patients with CML-CP,” he added.
The group previously reported that dasatinib’s safety and efficacy profiles in paediatric patients with imatinib-pretreated CML compared favourably with those in adults, with 82 percent achieving complete cytogenetic response and 47 percent achieving major molecular response. [J Clin Oncol 2013;31:2460-2468]
In the pre-tyrosine kinase inhibitor (TKI) era, adults with CML treated with hydroxycarbamide or interferon-alpha (IFN-α) had a 10-year survival rate of 5 percent. [Br J Haematol 2014;167:33-47]
Recently, complete responses have been documented with TKIs directed against BCR-ABL (the fusion gene characteristic of CML), such as imatinib. Imatinib is now the standard treatment for most patients with CML. However, intolerance or resistance to imatinib treatment is still high (around 30 percent). [Korean J Pediatr 2011;54:111-116]