FDA Approves Nilotinib for Frontline and Secondline Use in Pediatric CML

The FDA approved nilotinib for first- and secondline use in pediatric patients (≥1 year) with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CP-CML).

Approval was based on results of two open-label, single-arm, multicenter trials (CAMN107A2120 and CAMN107A2203) that included 69 pediatric patients (25 newly diagnosed and 44 previously treated, including those resistant to tyrosine kinase inhibitors) with Ph+ CP-CML. In both trials, patients received nilotinib 230 mg/m2 twice-daily, rounded to the nearest 50 mg dose (maximum single dose of 400 mg) in 28-day treatment cycles (the recommended pediatric dose). The median time on treatment was 13.8 months (range = 0.7-30.9 months).

The major molecular response rate was 40.9 percent (n=18/44; 95% CI 26.3-56.8) at 12 cycles in patients with resistant or intolerant disease, and 60.0 percent (n=15/25; 95% CI 38.7-78.9) at 12 cycles in those with newly diagnosed Ph+ CP-CML.

Among patients with resistant or intolerant disease, 4.5 percent achieved deep molecular response (MR4.5), while 28.0 percent of those with newly diagnosed CML achieved MR4.5.

The most common AEs associated with nilotinib are hyperbilirubinemia, thrombocytopenia, rash, neutropenia, lymphopenia, increased alanine (ALT) and aspartate aminotransferase, headache, anemia, pyrexia, nausea, upper respiratory tract infection, and vomiting. The most common grade 3/4 AEs were increased ALT and hyperbilirubinemia.

Nilotinib previously received priority review and orphan-drug designation for this indication. The drug also has been FDA-approved for first- and secondline use in adults with Ph+ CP-CML.

Source: U.S. Food and Drug Administration press release, March 22, 2018.