Eleutherakis-Papaiakovou Evangelos, Kanellias Nikolaos, Kastritis Efstathios, Gavriatopoulou Maria, Terpos Evangelos, Dimopoulos Meletios Athanasios
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece.
J Oncol. 2020 Jan 13;2020:7131802. doi: 10.1155/2020/7131802. eCollection 2020.
Panobinostat represents a potent oral nonselective pan-histone deacetylase inhibitor (HDAC) with activity in myeloma patients. It has been approved by the FDA and EMA in combination with bortezomib and dexamethasone for the treatment of multiple myeloma, in patients who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. In order to further explore its clinical potential, it is evaluated in different combinations in relapsed/refractory and newly diagnosed multiple myeloma. This review focuses on available data about panobinostat's pharmacology and its role in clinical practice. This review will reveal panobinostat's efficacy as antimyeloma treatment, describing drug evolution from preclinical experimental administration to administration in phase III trials, which established its role in current clinical practice. Based on the latest data, we will present its mechanism of action, its efficacy, and most important issues regarding its toxicity profile. We will further try to shed light on its role in current and future therapeutic landscape of myeloma patients. Panobinostat retains its role in therapy of multiple myeloma because of its manageable toxicity profile and its efficacy, mainly in heavily pretreated multiple myeloma patients. These characteristics make it valuable also for novel regimens in combination with second-generation proteasome inhibitors, IMiDs, and monoclonal antibodies. Results of ongoing trials are expected to shed light on drug introduction in different therapeutic combinations or even at an earlier level of disease course.
帕比司他是一种有效的口服非选择性泛组蛋白去乙酰化酶抑制剂（HDAC），对骨髓瘤患者具有活性。它已获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准，与硼替佐米和地塞米松联合用于治疗接受过至少两种包括硼替佐米和一种免疫调节剂在内的先前治疗方案的多发性骨髓瘤患者。为了进一步探索其临床潜力，正在复发/难治性和新诊断的多发性骨髓瘤中对其不同联合用药方案进行评估。本综述重点关注有关帕比司他药理学及其在临床实践中作用的现有数据。本综述将揭示帕比司他作为抗骨髓瘤治疗的疗效，描述从临床前实验给药到III期试验给药的药物演变过程，这确立了其在当前临床实践中的作用。基于最新数据，我们将介绍其作用机制、疗效以及关于其毒性特征的最重要问题。我们还将进一步阐明其在骨髓瘤患者当前和未来治疗格局中的作用。帕比司他因其可控的毒性特征和疗效，在多发性骨髓瘤治疗中仍保留其作用，主要是在经过大量预处理的多发性骨髓瘤患者中。这些特性使其对于与第二代蛋白酶体抑制剂、免疫调节药物（IMiDs）和单克隆抗体联合的新方案也具有价值。正在进行的试验结果有望为不同治疗联合方案甚至疾病进程早期引入该药物提供线索。
