Gao Xiao, Shen Lijing, Li Xiang, Liu Jiaying
Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1057-1068. doi: 10.3892/etm.2019.7704. Epub 2019 Jun 25.
Multiple myeloma (MM) remains incurable primarily due to relapse. Histone deacetylase inhibitors (HDACis) have shown potential application for the treatment of relapsed/refractory multiple myeloma (RRMM). To assess the efficacy and safety of HDACis in RRMM treatment, a systematic review and meta-analysis were conducted based on clinical trial data. A literature search was performed using PubMed, EMBASE, Web of Science and the Cochrane Library databases. Subsequently, 19 trials with 2193 patients treated with one of the three HDACis, panobinostat, ricolinostat and vorinostat, were identified and included in the present study. The efficacy and toxicity of each agent were assessed. The data were pooled using a random effects model in STATA 13.0. The results showed that the overall response rate (ORR) was 0.64 with a 95% confidence interval (CI) of 0.61-0.68 for panobinostat, 0.51 (95% CI, 0.46-0.55) for vorinostat and 0.38 (95% CI, 0.29-0.48) for ricolinostat. Additionally, subgroup analysis revealed an ORR of 0.36 (95% CI, 0.27-0.46) for HDACis-treated bortezomib-refractory MM patients and 0.43 (95% CI, 0.30-0.55) for lenalidomide-refractory patients. The most common grade 3 and 4 hematological adverse events were thrombocytopenia, neutropenia and anemia. Non-hematological adverse events included fatigue/asthenia, diarrhea and nausea. In conclusion, analysis of the pooled data revealed that panobinostat-containing regimens were effective and tolerable for patients with RRMM. Furthermore, lenalidomide-refractory patients may derive greater benefits from these regimens. More clinical and real-world studies are required to validate these results.
多发性骨髓瘤（MM）主要由于复发而仍然无法治愈。组蛋白去乙酰化酶抑制剂（HDACis）已显示出在治疗复发/难治性多发性骨髓瘤（RRMM）中的潜在应用。为了评估HDACis在RRMM治疗中的疗效和安全性，基于临床试验数据进行了系统评价和荟萃分析。使用PubMed、EMBASE、科学网和考克兰图书馆数据库进行文献检索。随后，确定了19项试验，共2193例接受三种HDACis之一（帕比司他、瑞可利司他和伏立诺他）治疗的患者，并纳入本研究。评估了每种药物的疗效和毒性。数据在STATA 13.0中使用随机效应模型进行汇总。结果显示，帕比司他的总缓解率（ORR）为0.64，95%置信区间（CI）为0.61 - 0.68；伏立诺他为0.51（95%CI，0.46 - 0.55）；瑞可利司他为0.38（95%CI，0.29 - 0.48）。此外，亚组分析显示，接受HDACis治疗的硼替佐米难治性MM患者的ORR为0.36（95%CI，0.27 - 0.46），来那度胺难治性患者为0.43（95%CI，0.30 - 0.55）。最常见的3级和4级血液学不良事件是血小板减少、中性粒细胞减少和贫血。非血液学不良事件包括疲劳/乏力、腹泻和恶心。总之，汇总数据分析显示，含帕比司他的方案对RRMM患者有效且耐受性良好。此外，来那度胺难治性患者可能从这些方案中获得更大益处。需要更多的临床和真实世界研究来验证这些结果。
