Oliva Esther Natalie, Ronnebaum Sarah M, Zaidi Omer, Patel Dipen A, Nehme Salem Abi, Chen Clara, Almeida Antonio M
Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli Reggio Calabria, Italy.
OPEN Health Bethesda, MD, USA.
Am J Blood Res. 2021 Aug 15;11(4):325-360. eCollection 2021.
Acute myeloid leukemia (AML) is a rapidly progressive hematological malignancy that is difficult to cure. The prognosis is poor and treatment options are limited in case of relapse. A comprehensive assessment of current disease burden and the clinical efficacy of non-intensive therapies in this population are lacking. We conducted two systematic literature reviews (SLRs). The first SLR (disease burden) included observational studies reporting the incidence and economic and humanistic burden of relapsed/refractory (RR) AML. The second SLR (clinical efficacy) included clinical trials (phase II or later) reporting remission rates (complete remission [CR] or CR with incomplete hematologic recovery [CRi]) and median overall survival (mOS) in patients with RR AML or patients with AML who are ineligible for intensive chemotherapy. For both SLRs, MEDLINE/Embase were searched from January 1, 2008 to January 31, 2020. Clinical trial registries were also searched for the clinical efficacy SLR. After screening, two independent reviewers determined the eligibility for inclusion in the SLRs based on full-text articles. The disease burden SLR identified 130 observational studies. The median cumulative incidence of relapse was 29.4% after stem cell transplant and 46.8% after induction chemotherapy. Total per-patient-per-month costs were $28,148-$29,322; costs and health care resource use were typically higher for RR versus non-RR patients. Patients with RR AML had worse health-related quality of life (HRQoL) scores than patients with AML across multiple instruments, and lower health utility values versus other AML health states (i.e. newly diagnosed, remission, consolidation, and maintenance therapy). The clinical efficacy SLR identified 50 trials (66 total trial arms). CR/CRi rates and mOS have remained relatively stable and low over the last 2 decades. Across all arms, the median rate of CR/CRi was 18.3% and mOS was 6.2 months. In conclusion, a substantial proportion of patients with AML will develop RR AML, which is associated with significant humanistic and economic burden. Existing treatments offer limited efficacy, highlighting the need for more effective non-intensive treatment options.
急性髓系白血病（AML）是一种进展迅速的血液系统恶性肿瘤，难以治愈。预后较差，复发时的治疗选择有限。目前缺乏对该人群当前疾病负担以及非强化治疗临床疗效的全面评估。我们进行了两项系统文献综述（SLR）。第一项SLR（疾病负担）纳入了报告复发/难治性（RR）AML发病率以及经济和人文负担的观察性研究。第二项SLR（临床疗效）纳入了报告RR AML患者或不符合强化化疗条件的AML患者缓解率（完全缓解[CR]或伴有血液学未完全恢复的CR[CRi]）及中位总生存期（mOS）的临床试验（II期或更后期）。对于这两项SLR，检索了2008年1月1日至2020年1月31日期间的MEDLINE/Embase。还检索了临床试验注册库以获取临床疗效SLR的相关信息。筛选后，两名独立评审员根据全文文章确定纳入SLR的资格。疾病负担SLR共识别出130项观察性研究。干细胞移植后复发的中位累积发生率为29.4%，诱导化疗后为46.8%。每位患者每月的总费用为28,148美元至29,322美元；RR患者的费用和医疗资源使用通常高于非RR患者。与多种工具评估的AML患者相比，RR AML患者的健康相关生活质量（HRQoL）得分更低，与其他AML健康状态（即新诊断、缓解、巩固和维持治疗）相比，健康效用值也更低。临床疗效SLR共识别出50项试验（总计66个试验组）。在过去20年中，CR/CRi率和mOS一直相对稳定且较低。在所有试验组中，CR/CRi的中位率为18.3%，mOS为6.2个月。总之，相当一部分AML患者会发展为RR AML，这与巨大的人文和经济负担相关。现有治疗的疗效有限，凸显了对更有效的非强化治疗选择的需求。
