On March 22, the U.S. Food and Drug Administration (FDA) expanded the indication for nilotinib (Tasigna) to include treatment of first- and second-line pediatric patients 1 year of age or older with Philadelphia chromosome–positive chronic myeloid leukemia (CML) in the chronic phase.
In the United States, nilotinib is now indicated for the treatment of adult and pediatric patients 1 year of age or older with newly diagnosed Philadelphia chromosome–positive chronic-phase CML. Nilotinib is also indicated for the treatment of pediatric patients 1 year of age or older with Philadelphia chromosome–positive chronic-phase CML that is resistant or intolerant to prior tyrosine kinase inhibitor therapy, as well as adult patients with Philadelphia chromosome–positive CML in chronic phase and accelerated-phase resistant or intolerant to prior therapy that included imatinib.
Clinical Trials
The new indications, granted under the FDA’s Priority Review designation, are based on two studies evaluating the efficacy and safety of nilotinib in pediatric patients (2 years to less than 18 years of age) with Philadelphia chromosome–positive chronic-phase CML. A total of 69 pediatric patients with Philadelphia chromosome–positive chronic-phase CML, either newly diagnosed (first-line) or who were resistant or intolerant to prior tyrosine kinase inhibitor therapy (second-line), received nilotinib. In newly diagnosed pediatric patients, the major molecular response (MMR; BCR ABL/ABL ≤ 0.1% International Scale) rate was 60.0% (95% confidence interval [CI] = 38.7%–78.9%) at 12 cycles, with 15 patients achieving MMR. The cumulative MMR rate among newly diagnosed pediatric patients was 64.0% by cycle 12, and the median time to first MMR was 5.6 months (range, 2.7–16.6 months). In pediatric patients with resistance or intolerance to prior TKI therapy, the MMR rate was 40.9% (95% CI = 26.3%–56.8%) at 12 cycles, with 18 patients being in MMR. The cumulative MMR rate among pediatric patients with resistance or intolerance was 47.7% by cycle 12, and the median time to first MMR was 2.8 months (range, 0.0–11.3 months).
Adverse reactions observed in these pediatric studies were generally consistent with those observed in adults, except for laboratory abnormalities of hyperbilirubinemia (grade 3/4, 13%) and transaminase elevation (aspartate transaminase grade 3/4, 1%; alanine transaminase grade 3/4, 9%), which were reported at a higher frequency than in adult patients. One resistant or intolerant pediatric CML patient progressed to advance phase/blast crisis after about 10 months on treatment. ■
