Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen Bonn Cologne Düsseldorf, Germany.
Leuk Res. 2024 Apr;139:107481. doi: 10.1016/j.leukres.2024.107481. Epub 2024 Mar 11.
The BYOND study evaluated the efficacy and safety of bosutinib 500 mg once daily in patients with chronic myeloid leukemia (CML) resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). These post-hoc analyses assessed the efficacy and safety of bosutinib by resistance or intolerance to prior TKIs (imatinib-resistant vs dasatinib/nilotinib-resistant vs TKI-intolerant), and cross-intolerance between bosutinib and prior TKIs (imatinib, dasatinib, nilotinib), in patients with Philadelphia chromosome-positive chronic phase CML. Data are reported after ≥3 years' follow-up. Of 156 patients with Philadelphia chromosome-positive chronic phase CML, 53 were imatinib-resistant, 29 dasatinib/nilotinib-resistant, and 74 intolerant to all prior TKIs; cumulative complete cytogenetic response rates at any time were 83.7%, 61.5%, and 86.8%, and cumulative major molecular response rates at any time were 72.9%, 40.7%, and 82.4%, respectively. Of 141, 95, and 79 patients who received prior imatinib, dasatinib, and nilotinib, 64 (45.4%), 71 (74.7%), and 60 (75.9%) discontinued the respective TKI due to intolerance; of these, 2 (3.1%), 5 (7.0%), and 0 had cross-intolerance with bosutinib. The response rates observed in TKI-resistant and TKI-intolerant patients, and low cross-intolerance between bosutinib and prior TKIs, further support bosutinib use for patients with Philadelphia chromosome-positive chronic phase CML resistant/intolerant to prior TKIs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02228382.
BYOND 研究评估了每日一次 500mg 博舒替尼用于先前对酪氨酸激酶抑制剂(TKI)耐药/不耐受的慢性髓性白血病(CML)患者的疗效和安全性。这些事后分析根据先前 TKI(伊马替尼耐药 vs 达沙替尼/尼洛替尼耐药 vs TKI 不耐受)的耐药或不耐受评估了博舒替尼的疗效和安全性,并评估了博舒替尼与先前 TKI(伊马替尼、达沙替尼、尼洛替尼)之间的交叉不耐受性,在费城染色体阳性慢性期 CML 患者中。数据报告随访时间≥3 年后。在 156 例费城染色体阳性慢性期 CML 患者中,53 例对伊马替尼耐药,29 例对达沙替尼/尼洛替尼耐药,74 例对所有先前 TKI 不耐受;任何时候完全细胞遗传学缓解率分别为 83.7%、61.5%和 86.8%,任何时候主要分子学缓解率分别为 72.9%、40.7%和 82.4%。在先前接受伊马替尼、达沙替尼和尼洛替尼治疗的 141、95 和 79 例患者中,分别有 64(45.4%)、71(74.7%)和 60(75.9%)因不耐受而停用各自的 TKI;其中,2(3.1%)、5(7.0%)和 0 例患者对博舒替尼有交叉不耐受。在 TKI 耐药和 TKI 不耐受患者中观察到的缓解率以及博舒替尼与先前 TKI 之间的低交叉不耐受性,进一步支持博舒替尼用于先前对 TKI 耐药/不耐受的费城染色体阳性慢性期 CML 患者。临床试验注册:ClinicalTrials.gov:NCT02228382。