奥雷巴替尼治疗慢性髓系白血病的研究进展

Research Progress of Olverembatinib in the Treatment of Chronic Myeloid Leukemia

在慢性粒细胞白血病患者中,野生型及发生继发性突变的BCR-ABL1融合基因,会激活下游信号通路,导致癌症的发生。然而BCR-ABL1的突变赋予了耐药的发生,潜在影响了酪氨酸激酶抑制剂治疗慢粒的有效性。其中,突变率最高的是T315I,它对所有的一代、二代TKI耐药,虽普纳替尼与阿西米尼对其有一定的疗效,但普纳替尼较高的副反应发生率,如心血管毒性及肝毒性,仍让一部分患者陷入困境,且两者均未在中国上市,购买不易。因此,由我国研制的第三代酪氨酸激酶抑制剂奥雷巴替尼,解决了我国伴T315I突变的慢粒患者的治疗空白。奥雷巴替尼在目前的临床试验中展现出了良好的有效性和安全性,未来是值得期待的。

In patients with chronic myeloid leukemia, wild type and secondary mutation of BCR::ABL1 fusion gene can activate downstream signaling pathways, leading to the occurrence of cancer. However, mutations in BCR::ABL1 confer resistance, potentially affecting the effectiveness of tyrosine kinase inhibitors in the treatment of CML. T315I has the highest mutation rate, which is resistant to all first-generation and second-generation TKIs. Ponatinib and asciminib have a certain effect on it, but the high incidence of side effects of ponatinib, such as cardiovascular toxicity and liver toxicity, still makes some patients in trouble. Neither is listed in China, making it difficult to buy. Therefore, the third-generation tyrosine kinase inhibitor Olverembatinib developed by China has solved the treatment gap of patients with CML with T315I mutation in China. In the current clinical trials, Ol-verembatinib has shown good efficacy and safety, and the future is worth looking forward to.