San-Miguel Jesus F, Einsele Hermann, Moreau Philippe
Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain.
Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany.
Adv Ther. 2016 Nov;33(11):1896-1920. doi: 10.1007/s12325-016-0413-7. Epub 2016 Sep 27.
Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received ≥2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population. The authorization and recommendation were based on results from the pivotal phase 3 PANORAMA 1 (NCT01023308) clinical trial, which demonstrated an improvement in median progression-free survival of 7.8 months for the three-drug combination compared with placebo plus bortezomib and dexamethasone in this patient population. This review will discuss the current treatment landscape for relapsed/refractory MM, the mechanism of action of panobinostat, clinical data supporting the European authorization, concerns about safety and strategies for mitigating toxicity, and how panobinostat fits into the current MM landscape in Europe.
Editorial support, funded by Novartis Pharmaceuticals.
帕比司他是诺华公司研发的一种口服泛组蛋白去乙酰化酶抑制剂。帕比司他通过表观遗传修饰和抑制聚集体途径发挥作用。2015年8月，欧盟委员会批准帕比司他与硼替佐米及地塞米松联合使用，用于治疗接受过≥2种包括硼替佐米和一种免疫调节药物的既往治疗方案的复发或复发难治性多发性骨髓瘤（MM）患者。2016年1月，英国国家卫生与临床优化研究所推荐帕比司他用于相同的联合治疗及患者群体。该批准和推荐基于关键的3期PANORAMA 1（NCT01023308）临床试验结果，该试验表明，在该患者群体中，与安慰剂加硼替佐米及地塞米松相比，三药联合治疗的中位无进展生存期改善了7.8个月。本综述将讨论复发/难治性MM的当前治疗格局、帕比司他的作用机制、支持欧盟批准的临床数据、对安全性的担忧及减轻毒性的策略，以及帕比司他如何融入欧洲当前的MM格局。
编辑支持，由诺华制药公司资助。
