Nilotinib approved for pediatric CML

March 22, 2018—Today, the U.S. Food and Drug Administration (FDA) expanded the approval of nilotinib to include the first- and second-line treatment of pediatric patients with chronic myeloid leukemia (CML). Nilotinib is now approved for patients aged 1 year and older with Philadelphia chromosome positive (Ph+) CML in the chronic phase that is newly diagnosed (first-line) or that is resistant or intolerant to previous treatment with a tyrosine-kinase inhibitor (second-line).

Nilotinib was previously approved for adult patients with newly diagnosed Ph+ CML in the chronic phase, as well as adult patients with chronic or accelerated phase disease who were resistant or otherwise intolerant to imatinib.

This expanded indication is based on results from 2 open-label, single-arm, multicenter trials: CAMN107A2120 (NCT01077544) in pediatric patients with Ph+ CML in the chronic phase who are resistant or intolerant to imatinib or dasatinib (n=11); and, CAMN107A2203 (NCT01844765) in pediatric patients with newly diagnosed Ph+ chronic phase CML (n=25) or who are resistant or intolerant to imatinib or dasatinib (n=33).

For patients receiving nilotinib in the second line, the major molecular response rate (MMR)—defined as a 3-log drop in BCR-ABL/ABL (≤ 0.1% International Scale)—was 40.9% at 12 cycles. The cumulative MMR rate in these patients was 47.7% by cycle 12 and the median time to first MMR was 2.8 months. In patients receiving nilotinib in the first line, the MMR rate was 60.0% at 12 cycles. The cumulative MMR rate in these patients was 64.0% by cycle 12 and the median time to first MMR was 5.6 months. Further, among patients with resistant or intolerant CML, 4.5% of patients achieved BCR-ABL/ABL ≤0.0032% International Scale (MR4.5) by the time of data cut-off. Among patients with newly diagnosed CML, this percentage was 28.0%.

Treatment-related toxicities were consistent with those observed in adult populations and the most common grade 3/4 adverse events (AEs) observed included alanine aminotransferase increase and hyperbilirubinemia. Other common AEs included thrombocytopenia, rash, neutropenia, lymphopenia, headache, anemia, pyrexia, nausea, upper respiratory tract infection, aspartate aminotransferase increased, and vomiting.

The recommended pediatric dose of nilotinib is 230 mg/m² orally twice daily, rounded to the nearest 50 mg dose, with a maximum single dose of 400 mg. Full prescribing information of nilotinib can be found here.

--
Jonathan A. Bell
Published Online: Thursday, March 22, 2018