Department of Transfusion and Cell Therapy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Department of Hematology, Nephrology, and Rheumatology, Akita University School of Medicine, Akita, Japan.
Cancer Sci. 2023 Mar;114(3):995-1006. doi: 10.1111/cas.15642. Epub 2022 Nov 23.
Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities. A total of 136 patients (30.1%) were classified into an older cohort (≥65 years) and 316 (69.9%) into a younger cohort (18-64 years). The TKI selection did not vary based on age (70.6% received 2GTKIs in the younger cohort and 66.2% in the older cohort). The median follow-up period was 5.4 years. Treatment responses including the cumulative incidence of deep molecular response (BCR-ABL1 international scale ≤0.0032%) at any time were similar between the two age cohorts regardless of the type of TKI. The 5-year overall survival (OS) in the older cohort was lower than that in the younger cohort (95.9% vs 83.8%; p < 0.0001), whereas the 5-year OS in patients treated with 2GTKIs was not influenced by age factors and comorbidities. Therefore, our results suggest that the selection of 2GTKIs as first-line treatment is an effective option for both younger and older CML-CP patients with or without comorbidities. This trial was registered at UMIN-CTR as 00003581.
年龄和合并症是选择酪氨酸激酶抑制剂 (TKI) 进行慢性髓性白血病慢性期 (CML-CP) 一线治疗的重要因素。然而,TKI 选择,特别是伊马替尼与第二代 TKI(2GTKI)的选择是否会影响临床实践中的治疗结果尚不清楚。为了解决这个问题,我们比较了前瞻性登记的 452 例 CML-CP 患者接受伊马替尼和 2GTKI 治疗的临床结果,同时考虑了他们的年龄和/或合并症。共有 136 例患者(30.1%)被归入老年队列(≥65 岁),316 例(69.9%)归入年轻队列(18-64 岁)。TKI 选择与年龄无关(年轻队列中有 70.6%接受了 2GTKI,老年队列中有 66.2%)。中位随访时间为 5.4 年。无论 TKI 类型如何,两个年龄队列的治疗反应(包括任何时间的深度分子反应累积发生率(BCR-ABL1 国际量表≤0.0032%))相似。老年队列的 5 年总生存(OS)低于年轻队列(95.9% vs 83.8%;p<0.0001),而 2GTKI 治疗患者的 5 年 OS 不受年龄因素和合并症的影响。因此,我们的结果表明,2GTKI 作为一线治疗的选择对于有或没有合并症的年轻和老年 CML-CP 患者都是有效的选择。该试验在 UMIN-CTR 注册为 00003581。