Kunacheewa Chutima, Thongthang Pakaporn, Ungprasert Patompong, Utchariyaprasit Eakkapol, Owattanapanich Weerapat
a Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital , Mahidol University , Bangkok , Thailand.
b Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital , Mahidol University , Bangkok , Thailand.
Hematology. 2019 Dec;24(1):498-506. doi: 10.1080/16078454.2019.1631425.
The addition of lenalidomide (LEN) to azacitidine (AZA) may further improve the outcomes of acute myeloid leukemia (AML) patients as well as patients with high-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients although the evidence for this combination treatment is still relatively limited. This meta-analysis aimed to evaluate efficacy and adverse effects of AZA plus LEN for the treatment of patients with high-risk MDS, AML or CMML.
The current study systematically identified all cohort studies of patients with AML and/or MDS and/or CMML who received AZA in combination with LEN that reported the overall complete remission (CR) rate and/or overall response rate (ORR). A DerSimonian-d random-effects model with double arcsine transformation was used for the pooled rates and 95% confidence interval (CI) of the all outcomes.
A total of 10 studies with 406 patients were identified and included into the meta-analysis. The pooled CR rate after the treatment with AZA-plus-LEN regimen was 33.0% (95% CI, 27.7%-38.7%, I = 18%) while the pooled ORR was 49.9% (95% CI, 38.4%-61.5%, I = 72%). Nonetheless, adverse events including grade 3-4 neutrophil toxicity events, platelet toxicity events and febrile neutropenia were common with AZA-plus-LEN regimen.
The current study may serve as a preliminary data to suggest that the addition of LEN may offer incremental benefit to patients with high-risk MDS, AML and CMML. However, randomized-controlled studies that directly compare the efficacy and adverse events of AZA-plus-LEN regimen versus AZA monotherapy are still needed.
尽管来那度胺(LEN)联合阿扎胞苷(AZA)治疗急性髓系白血病(AML)患者、高危骨髓增生异常综合征(MDS)患者及慢性粒单核细胞白血病(CMML)患者的证据仍相对有限,但这种联合治疗可能进一步改善这些患者的预后。本荟萃分析旨在评估AZA联合LEN治疗高危MDS、AML或CMML患者的疗效及不良反应。
本研究系统检索了所有关于接受AZA联合LEN治疗的AML和/或MDS和/或CMML患者的队列研究,这些研究报告了总体完全缓解(CR)率和/或总体缓解率(ORR)。采用双反正弦变换的DerSimonian-Laird随机效应模型计算所有结局的合并率及95%置信区间(CI)。
共纳入10项研究,406例患者,进行荟萃分析。AZA联合LEN方案治疗后的合并CR率为33.0%(95%CI,27.7%-38.7%,I² = 18%),合并ORR为49.9%(95%CI,38.4%-61.5%,I² = 72%)。然而,AZA联合LEN方案常见3-4级中性粒细胞毒性事件、血小板毒性事件和发热性中性粒细胞减少等不良事件。
本研究可作为初步数据提示,添加LEN可能为高危MDS、AML和CMML患者带来额外益处。然而,仍需要直接比较AZA联合LEN方案与AZA单药治疗的疗效和不良事件的随机对照研究。