TKI Safe and Effective in Pediatric CML

Submitted by admin5 on Thu, 06/15/2017 - 14:00

A recent study demonstrated high response rates and tolerable safety profiles in pediatric patients with chronic myeloid leukemia (CML) after treatment with a tyrosine kinase inhibitor (TKI).


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Imatinib is currently the only approved option for pediatric patients with CML. The blood disorder is relatively rare—representing less than 3% of all leukemias worldwide—which makes it difficult to study. There is an overwhelming unmet need for pediatric patients with CML.

Lia Gore, MD, University of Colorado at Denver, and colleagues conducted a phase II CA-180-226 trial to assess the efficacy of dasatinib in imatinib-refractory or imatinib-intolerant pediatric CML. Researchers conducted their study through two separate cohorts involving patients aged 18 or younger. Dasatinib has previously been approved for adult patients with CML, though not for pediatric patients. They presented their findings at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting earlier this month.

The first cohort consisted of 29 patients with CML chronic-phase who were imatinib-refractory or -intolerant. Patients were treated with a dasatinib tablet. The second cohort, which consisted of 84 newly diagnosed CML patients, were treated with dasatinib tablets (n = 51) or powdered formulation for oral suspension (PFOS, n = 33).

The results showed that after 3 months, the refractory or intolerant cohort exceeded the major cytogenetic response (MCyR) rate of clinical interest of 30%. By 24 months, the rate of MCyR exceeded 90%. The median time to response in these patients was 3.1 months, and the median duration of response had not been reached, according to the researchers.

The clinical rate of interest for complete cytogenetic response (CCyR) was 55% for newly diagnosed patients and was exceeded by 6 months. The CCyR rate was 94% by 24 months, and rates for both the tablet and powdered formulation for oral suspension forms of dasatinib both exceeded 90%.

The researchers observed a cumulative rate of major molecular response of 55% in refractory or intolerant patients and 70% in newly diagnosed patients (75% with tablet, 64% with powdered formulation for oral suspension) at 24 months. By 48 months, the progression-free survival rate was 78% in the refractory or intolerant patients and 93% in the newly diagnosed patients, while the median progression-free survival had not been reached.

“In the largest prospective trial of pediatric [patients] with CML [in chronic phase], target responses were met early and increased over time with [dasatinib] treatment,” the researchers concluded. “The efficacy and safety of [dasatinib] were consistent with previous reports in adults, except no cases of pleural/pericardial effusion or PAH were observed. These results suggest [dasatinib] is safe and highly effective in the first- or second-line treatment of pediatric CML [in chronic phase].” —Christina Vogt