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Addressing Off-Target Effects of TKIs in Pediatric CML

Angelica Welch
Published: Monday, Dec 10, 2018

blood cellsIn early 2018, the tyrosine kinase inhibitor (TKI) nilotinib (Tasigna) joined imatinib (Gleevec) and dasatinib (Sprycel) as a treatment for pediatric patients with chronic myeloid leukemia (CML).

TKIs are currently the go-to treatment for these patients, as they are known to have a survival benefit, explained Briana Patterson, MD. However, there have been some concerns on the impact of TKI therapy on the endocrine systems of growing children. These off-target effects can stunt growth and may impact the reproductive system, she explained.

In an interview with OncLive, Patterson, an assistant professor in the Division of Endocrinology, Aflac Cancer Center, Department of Pediatrics, Emory University School of Medicine, discussed the off-target effects of TKIs in pediatric patients with CML.

OncLive: What is the prevalence of TKI use in children? 

Patterson: Since the early 2000s when TKIs were first approved for pediatrics, imatinib has been used extensively in pediatric CML. Within the last year, dasatinib and nilotinib have been approved for pediatric use in CML. Those are considered first-line agents for chronic-phase CML in children now. For children who have more acute presentations, or other treatment considerations, whether they should receive a TKI or undergo transplant is a question for the oncologist. For children who present with chronic-phase CML, a first- or second-generation TKI will be the drug of choice.

What is the concern with endocrine effects of TKIs in children?

Everyone became interested in this quite a few years ago. Imatinib was initially released to treat adults with CML, and was later approved to treat pediatric patients with CML. That drastically changed the way that we approach children with CML, and it greatly improved survival. However, as a class, TKIs have a lot of off-target effects.

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