Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey

Objectives: We evaluated azacitidine (Vidaza®) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. Methods: This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010–2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. Results: The median age of patients was 74·7 (range: 43·9–87·8) years; 69·4% had MDS, 26·5% had primary or secondary AML, and 4·1% had CMML. Treatment-related TEAEs, grade 3–4 TEAEs, and TESAEs were reported in 67·3%, 28·6%, and 18·4% of patients, respectively. During 1YOP, patients received a median of 7 (1–12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n = 29), 41·4% had CR, PR, or HI, 41·4% had SD, and 17·2% had TF. Among AML patients (n = 9), 44·4% had CR or PR, 33·3% had SD, and 22·2% had TF. TI was observed in 14/32 (43·8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326–555) days; 1-year OS estimate was 0·571 (0·422–0·696). Conclusions: Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.

研究目的：本研究在真实世界场景中评估阿扎胞苷（azacitidine，商品名Vidaza®）用于骨髓增生异常综合征（myelodysplastic syndrome, MDS）、急性髓系白血病（acute myeloid leukaemia, AML）及慢性粒单核细胞白血病（chronic myelomonocytic leukaemia, CMML）患者的安全性与有效性，并对治疗应答、给药剂量及给药方案进行评估。
研究方法：本项非干预性上市后调查于2010年至2012年间在比利时14家血液学中心开展，共纳入50名接受阿扎胞苷治疗的患者中的49名。研究全程记录治疗突发不良事件（treatment-emergent adverse events, TEAEs），包括治疗相关TEAEs及严重TEAEs（serious TEAEs, TESAEs）。在1年观察期（1-year observation period, 1YOP）结束时或治疗中断时，评估治疗应答[完全缓解（complete response, CR）、部分缓解（partial response, PR）、血液学改善（haematological improvement, HI）、疾病稳定（stable disease, SD）、治疗失败（treatment failure, TF）]及输血不依赖（transfusion-independence, TI）；在研究结束时评估总生存期（overall survival, OS）。
研究结果：患者中位年龄为74.7（范围：43.9~87.8）岁；其中69.4%患有MDS，26.5%患有原发或继发AML，4.1%患有CMML。分别有67.3%、28.6%及18.4%的患者报告了治疗相关TEAEs、3~4级TEAEs及TESAEs。在1YOP期间，患者中位治疗周期数为7（范围：1~12）。共对49名患者中的38名评估了治疗应答。在MDS及CMML患者（n=29）中，41.4%达到CR、PR或HI，41.4%达到SD，17.2%出现TF；在AML患者（n=9）中，44.4%达到CR或PR，33.3%达到SD，22.2%出现TF。基线时依赖输血的患者中，14/32（43.8%）实现TI。中位总生存期（95%置信区间）为490（326~555）天；1年总生存期估算值为0.571（0.422~0.696）。
研究结论：本研究数据支持既往研究结论，即阿扎胞苷具有临床可接受的安全性特征，并展现出明确的抗肿瘤疗效。