First-line imatinib highly effective for paediatric chronic myeloid leukaemia
Use of imatinib in the first-line treatment of children and adolescents with chronic myeloid leukaemia (CML) appears highly effective, yielding excellent response with tolerable side effects, according to the results of a single-arm phase III trial.
The trial included 156 children (median age 13.2 years; 58.3 percent male) with newly diagnosed CML. Those with chronic phase (CP; n=146), accelerated phase (AP; n=3) and blastic phase (BP; n=7) disease received imatinib up-front at respective doses of 300, 400 and 500 mg/m2. Outcomes were evaluated in 148 patients with complete data (CP, n=140; AP, n=3; BP, n=5), with efficacy described only in the CML-CP group.
Event-free survival rate at 18 months was 97 percent (95 percent CI, 94.2−99.9) in the CML-CP group (median follow-up, 25 months). A total of 98 percent achieved complete haematologic response by month 3, 63 percent had complete cytogenetic response (CCyR) by month 12, and 59 percent had major molecular response (MMR) by month 18. [Leukemia 2018;32:1657-1669]
At 36 months, 86 percent of the patients achieved CCyR and 74 percent attained MMR. Treatment failure occurred in 38 patients (27 percent) due to unsatisfactory response or intolerance (n=9).
In the subgroup of 28 patients (19 percent) who underwent stem cell transplantation (SCT), five died of relapse (n=3) or SCT-related complications (n=2).
Adverse events (AEs) occurred in 98 of 148 patients (66 percent), with anaemia being the most common. Neutropoenia and gastrointestinal toxicity were the most frequently reported haematologic and nonhaematologic AEs (15 percent and 38 percent, respectively).
“This large paediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective,” the investigators said. [J Clin Oncol 2011;29:2827-2832; Pediatr Blood Cancer 2011;57:56-62; Blood 2004;104:2655-2660]
“The introduction of TKIs [tyrosine-kinase inhibitors] has marked an important and hopefully revolutionary step,” they continued. Notably, its use in the first-line setting prevents major SCT complications, such as transplant-related mortality and chronic graft-versus-host disease.
“However, only careful follow-up on long-term imatinib will provide information on the sustainability of responses, rates of resistance development and treatment-related complications, especially when transition from a paediatric setting into adult haematology becomes mandatory,” the investigators noted.