急性髓细胞白血病患者初次治疗草酰胞苷、伊达比星和阿拉-C（CLIA）联合索拉非尼与不联合索拉非尼的二期研究。
Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia.
发表日期：2023 Aug 27
作者：
Tapan M Kadia, Farhad Ravandi, Matteo Molica, Alex Bataller, Gautam Borthakur, Naval Daver, Elias Jabbour, Courtney D DiNardo, Naveen Pemmaraju, Nitin Jain, Alessandra Ferrajoli, Musa Ylimaz, Prithviraj Bose, Rebecca Slack Tidwell, Kayleigh R Marx, Caitlin R Rausch, Rashmi Kanagal-Shamanna, Sa Wang, Rabiul Islam, Richard Champlin, Elizabeth Shpall, Marina Konopleva, Guillermo Garcia-Manero, Hagop Kantarjian
来源：
AMERICAN JOURNAL OF HEMATOLOGY
摘要：
干扰素鸟苷酸（cladribine）或索拉非尼（sorafenib）与标准化疗联合应用已证明在新诊断的急性髓系白血病（AML）患者中提高了生存率。我们研究了克罗比滨（cladribine）、依柔比星（idarubicin）和中等剂量阿糖胞嘧啶（cytarabine）（CLIA）的联合用于年龄≤65岁、适合接受强化疗法的新诊断的AML患者。克罗比滨（5 mg/m2）静脉注射于1-5天，阿糖胞嘧啶（1 g/m2）于1-5天，依柔比星（10 mg/m2）于1-3天。对FLT3-ITD突变的AML患者加用索拉非尼于CLIA基础上。共招募了80例患者：65例新诊断的AML患者和15例治疗前骨髓增生异常综合征（ts-AML）所致的AML患者。中位年龄为55岁（范围，21-65）。未经治疗组和ts-AML组的CR+CRi分别为83％（54/65）和27％；分别有74％和75％的反应患者可检测不到的残留病变。接受CLIA+sorafenib治疗的FLT3-ITD突变AML患者中，CR+CRi率为95％，81％的患者MRD为阴性。随访中位数为76个月，2年和4年的总生存率分别为57％和50％，而ts-AML分别为20％和13％。接受CLIA+sorafenib治疗的患者的2年和5年总生存率分别为63％和59％。最常见的≥3级不良事件是感染/发热、胆红素升高、皮疹和恶心。对于新诊断的适合年轻患者的AML，CLIA是安全有效的，而ts-AML患者的结果较差。在FLT3-ITD突变的AML中，将索拉非尼加入CLIA可获得高持续缓解率和优异的长期生存率。©2023 Wiley Periodicals LLC.
The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1-5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). The median age was 55 years (range, 21-65). CR + CRi was 83% (54/65) and 27% in the untreated and ts-AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.© 2023 Wiley Periodicals LLC.