Radotinib and its clinical potential in chronic-phase chronic myeloid leukemia patients: an update

Abstract

Abstract:Although imatinib has dramatically improved major outcomes in patients with chronic myeloid leukemia (CML), there are newer tyrosine kinase inhibitors (TKIs) approved worldwide for the treatment of resistant cases, and two second-generation TKIs (dasatinib, nilotinib) are approved in some nations for treating patients in the upfront setting. Radotinib (IY5511HCL, Supect®) is a novel and selective second-generation BCR-ABL1 TKI, which is currently approved in Korea for the treatment of patients with CML both in the upfront and salvage settings. This review mainly focuses on the clinical potential of radotinib in patients with CML in chronic phase in terms of efficacy and safety.

Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia—From Molecular Mechanisms to Clinical Relevance

“…Nilotinib is resistant to Y253H/F, E255K/V, and T315I [ 27 , 34 , 35 , 93 ] but is an alternative for second line treatment in cases of other mutations. Very similar to Nilotinib, the Korean approved TKI (Radotinib) presented an in vitro IC 50 of 34 nM [ 41 , 239 ]. Nevertheless, cases of Radotinib resistance have been associated with BCR-ABL1 point mutations, namely Y235H, E255V, T315I, and T315M [ 239 ] ( Table 1 ).…”

“…Very similar to Nilotinib, the Korean approved TKI (Radotinib) presented an in vitro IC 50 of 34 nM [ 41 , 239 ]. Nevertheless, cases of Radotinib resistance have been associated with BCR-ABL1 point mutations, namely Y235H, E255V, T315I, and T315M [ 239 ] ( Table 1 ). Bosutinib, a second-generation TKI, is a dual SRC/ABL1 kinase inhibitor that binds to BCR-ABL1 in both conformations, as described for Dasatinib [ 240 , 241 ].…”

Moving on from 2013 to 2020 European LeukemiaNet recommendations for treating chronic myeloid leukemia: what has changed over the 7 years?

“…This follows the data from the BFORE trial published in 2018 that compares bosutinib to imatinib in newly diagnosed CML-CP patients [10,11]. The panel recognized radotinib [12] and its randomized comparison with imatinib in Korea [13] but, concluded that further information is needed for this drug before its universal recommendation for treatment. Asciminib is mentioned as a potential future treatment option.…”

Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression

“…[13][14][15] Radotinib is approved in South Korea as a secondline treatment for chronic phase chronic myeloid leukemia (CML-CP). 16,17 It inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. 16,18 Recently, Phase III clinical trial on the efficacy and safety of radotinib demonstrated its superiority over imatinib in generating complete cytogenetic response and major molecular response in patients newly evaluated with Philadelphia chromosomepositive CML-CP.…”