Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors.

Abstract

Radotinib (IY5511HCL), a novel and selective BCR-ABL1 tyrosine kinase inhibitor,

has shown pre-clinical and phase I activity and safety in chronic myeloid

leukemia. This phase II study investigated the efficacy and safety of radotinib

in Philadelphia chromosome-positive chronic phase-chronic myeloid leukemia

patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase

inhibitors. Patients received radotinib 400 mg twice daily for 12 cycles based on

results from the phase I trial. The primary end point was rate of major

cytogenetic response by 12 months. A total of 77 patients were enrolled. Major

cytogenetic response was achieved in 50 (65%; cumulative 75%) patients, including

36 (47%) patients with complete cytogenetic response by 12 months. Median time to

major cytogenetic response and complete cytogenetic response were 85 days and 256

days, respectively. Major cytogenetic response and complete cytogenetic response

rates were similar between imatinib-resistant and imatinib-intolerant patients,

but were higher in patients without BCR-ABL1 mutations. Overall and

progression-free survival rates at 12 months were 96.1% and 86.3%, respectively.

All newly-occurring or worsening grade 3/4 hematologic abnormalities included

thrombocytopenia (24.7%) and anemia (5.2%); grade 3/4 drug-related

non-hematologic adverse events included fatigue (3.9%), asthenia (3.9%), and

nausea (2.6%). The most common biochemistry abnormality was hyperbilirubinemia

(grade 3/4 23.4%), and 12 of 18 cases were managed with dose modification. Study

findings suggest radotinib is effective and well tolerated in chronic

phase-chronic myeloid leukemia patients with resistance and/or intolerance to

BCR-ABL1 tyrosine kinase inhibitors and may represent a promising alternative for

these patients. (clinicaltrials.gov identifier: 01602952).