Boddu Prajwal Chaitanya, Kantarjian Hagop M, Ravandi Farhad, Garcia-Manero Guillermo, Verstovsek Srdan, Jabbour Elias J, Takahashi Koichi, Bhalla Kapil, Konopleva Marina, DiNardo Courtney D, Ohanian Maro, Pemmaraju Naveen, Jain Nitin, Pierce Sherry, Wierda William G, Cortes Jorge E, Kadia Tapan M
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2017 Aug 15;123(16):3050-3060. doi: 10.1002/cncr.30704. Epub 2017 Apr 7.
The development of newer strategies to improve outcomes for older patients with secondary acute myeloid leukemia (s-AML) is a critical unmet need. Establishing baseline metrics for evaluating newer approaches is important.
s-AML was defined as 1 or more of the following: a history of an antecedent hematologic disorder (AHD), a diagnosis of therapy-related acute myeloid leukemia (AML), and AML with karyotype abnormalities characteristic of myelodysplastic syndrome. Newly diagnosed s-AML patients aged 60 to 75 years were grouped into 5 treatment cohorts: 1) patients receiving high- or intermediate-dose cytarabine-based intensive chemotherapy (IC), 2) patients receiving a hypomethylating agent (HMA) or HMA combinations, 3) patients receiving low-dose cytarabine (LDAC) combinations, 4) patients receiving CPX-351, and 5) patients receiving investigational (INV) agents. Nine hundred thirty-one patients met the age and s-AML criteria.
Complete remission rates were statistically lower in the HMA group (36%) versus the IC (46%), CPX-351 (45%), and LDAC groups (43%). Patients receiving less intensive regimens (the HMA and LDAC groups combined) had superior overall survival (OS) in comparison with patients receiving IC-based regimens (median 6.9 vs 5.4 months; P = .048). Only 4.3% of the IC patients proceeded to transplantation, whereas 10.3% of the patients on lower intensity regimens did (P = .001). There was no difference in median survival between patients treated with CPX-351 and patients treated with conventional lower intensity approaches (P = .75). Age > 70 years, an adverse karyotype, and a prior AHD were associated with decreased OS in a multivariate analysis.
Lower intensity approaches are associated with lower early mortality rates and improved OS in comparison with intensive regimens. OS is poor with currently available therapies with a median OS of 6 months (5.4-7.6 months across regimens). Unsatisfactory outcomes with other INV agents underscore the need for more effective therapies. Cancer 2017;123:3050-60. © 2017 American Cancer Society.
制定新策略以改善老年继发性急性髓系白血病（s-AML）患者的治疗效果是一项迫切未被满足的需求。建立评估新方法的基线指标很重要。
s-AML定义为以下1种或多种情况：既往血液系统疾病史（AHD）、治疗相关急性髓系白血病（AML）诊断、以及具有骨髓增生异常综合征特征性核型异常的AML。年龄在60至75岁的新诊断s-AML患者被分为5个治疗队列：1）接受高剂量或中剂量阿糖胞苷强化化疗（IC）的患者；2）接受低甲基化药物（HMA）或HMA联合治疗的患者；3）接受低剂量阿糖胞苷（LDAC）联合治疗的患者；4）接受CPX-351治疗的患者；5）接受研究性（INV）药物治疗的患者。931例患者符合年龄和s-AML标准。
HMA组的完全缓解率（36%）在统计学上低于IC组（46%）、CPX-351组（45%）和LDAC组（43%）。与接受基于IC方案的患者相比，接受强度较低方案（HMA组和LDAC组合并）的患者总生存期（OS）更长（中位生存期6.9个月对5.4个月；P = 0.048）。只有4.3%的IC患者进行了移植，而强度较低方案组的患者为10.3%（P = 0.001）。接受CPX-351治疗的患者与接受传统低强度治疗方法的患者中位生存期无差异（P = 0.75）。多因素分析显示，年龄>70岁、不良核型和既往AHD与OS降低相关。
与强化方案相比，低强度治疗方法与较低的早期死亡率和改善的OS相关。目前可用疗法的OS较差，中位OS为6个月（各方案为5.4 - 7.6个月）。其他INV药物的治疗效果不理想凸显了对更有效疗法的需求。《癌症》2017年；123：3050 - 60。©2017美国癌症协会
