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

Sung Hyun Kim, Hari Menon, Saengsuree Jootar, Tapan Saikia, Jae Yong Kwak, Sang Kyun Sohn, Joon Seong Park, Seong Hyun Jeong, Hyeoung Joon Kim, Yeo Kyeoung Kim, Suk Joong Oh, Hawk Kim, Dae Young Zang, Joo Seop Chung, Ho Jin Shin, Young Rok Do, Jeong A. Kim, Dae Young Kim, Chul Won Choi, Sahee ParkHye Lin Park, Gong Yeal Lee, Dae Jin Cho, Jae Soo Shin, Dong Wook Kim

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34 Citations (Scopus)

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 nonhematologic 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).

Original languageEnglish
Pages (from-to)1191-1196
Number of pages6
JournalHaematologica
Volume99
Issue number7
DOIs
Publication statusPublished - 2014 Jul 1

ASJC Scopus subject areas

  • Hematology

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    Kim, S. H., Menon, H., Jootar, S., Saikia, T., Kwak, J. Y., Sohn, S. K., Park, J. S., Jeong, S. H., Kim, H. J., Kim, Y. K., Oh, S. J., Kim, H., Zang, D. Y., Chung, J. S., Shin, H. J., Do, Y. R., Kim, J. A., Kim, D. Y., Choi, C. W., ... Kim, D. W. (2014). Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Haematologica, 99(7), 1191-1196. https://doi.org/10.3324/haematol.2013.096776