Imatinib

Imatinib has shown a high level of activity in children with CML that is comparable with the activity observed in adults.[1,5-8] As a result of this high level of activity, it is common to initiate imatinib treatment in children with CML rather than proceeding immediately to allogeneic stem cell transplant.[9] The pharmacokinetics of imatinib in children appear consistent with previous results in adults.[10]

Doses of imatinib used in phase II trials for children with CML have ranged from 260 mg/m2 to 340 mg/m2, which provide comparable drug exposures as the adult flat-doses of 400 mg to 600 mg.[1,7,8]

Evidence (imatinib in children):

Early molecular responses, such as the polymerase chain reaction (PCR)–based minimal residual disease (MRD) measurement at 3 months of therapy showing 10% BCR::ABL1 fusion transcripts, have been reported to be associated with improved PFS, similar to early molecular response data in adults.[11] The European LeukemiaNet (ELN) has defined optimal molecular milestones of BCR::ABL1 transcript levels to be 10% or less at 3 months, 1% or less at 6 months, and 0.1% or less at 12 months or more of therapy.[12]

The monitoring parameters described for adults with CML are reasonable to use in children. Monitoring occurs every 3 months until MMR is achieved and confirmed every 3 to 6 months thereafter. For more information, see Chronic Myeloid Leukemia Treatment.

Imatinib is generally well tolerated in children. Adverse effects are generally mild to moderate and reversible with treatment discontinuation or dose reduction.[7,8] Growth delay occurs in most prepubertal children who receive imatinib.[13] Children who receive imatinib and experience growth impairment may show some catch-up growth during their pubertal growth spurts, but they are at risk of having lower-than-expected adult height, as most patients do not achieve midparental height.[13,14]