In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (p-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81–10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9–18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2–14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.
近年来，维奈克拉（VEN）联合去甲基化药物（HMAs）的治疗方案显著改善了不适合强化化疗的新诊断急性髓系白血病（AML）患者的预后，并在关键性随机对照试验VIALE-A结果公布后成为标准治疗方案。然而，VIALE-A研究中观察到的结果在多大程度上适用于真实世界环境仍不明确。为此，我们对接受一线VEN+HMA治疗、不适合强化诱导化疗的新诊断AML患者的真实世界研究进行了系统综述和荟萃分析，并将其生存结果与VIALE-A研究进行比较。我们从所有纳入研究中提取Kaplan-Meier曲线并重建个体生存数据，通过估计合并生存曲线，并采用时序检验与VIALE-A结果进行对比。我们还进行了二次分析，仅纳入使用VEN联合阿扎胞苷（AZA）方案的研究，因为该方案是VIALE-A原始研究采用的治疗方案。共有19项真实世界研究符合纳入标准并被纳入系统综述，其中大多数研究报道的生存结果逊于VIALE-A研究。合并生存曲线在治疗前三个月与VIALE-A报告结果相似，但此后出现显著差异（p值=0.0001）。真实世界研究的合并中位生存期为9.37个月（95%CI 8.81-10.5），显著低于VIALE-A报告的14.7个月（95%CI 11.9-18.7）。当分析限定于使用VEN+AZA方案的研究时，结果略有改善（中位生存期：11.5个月；95%CI 10.2-14.8）。真实世界环境中接受VEN+HMAs治疗的新诊断AML患者的生存期似乎低于VIALE-A先前报告的结果，而VEN+AZA方案的效果更符合预期。未来需要进一步研究评估这种差异是由于入组患者特征不同，还是治疗依从性未达最优所致，并探索替代方案能否在安全性和有效性方面提供更优结果。
肿瘤(癌症)患者之家