Hansen Vincent L, Coleman Morton, Elkins Stephanie, Letzer Jeffrey P, Levy Moshe Yair, Seneviratne Lasika, Rine Jessica, White Marina, Kuriakose Emil T
Northern Utah Associates, Ogden, UT.
Weill Cornell Medicine, Clinical Research Alliance, New York, NY.
Clin Lymphoma Myeloma Leuk. 2018 Jun;18(6):400-407.e1. doi: 10.1016/j.clml.2018.03.002. Epub 2018 Mar 14.
Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability.
In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1.3 mg/m twice weekly with dexamethasone 20 mg on the days of and after bortezomib treatment. Patients with no change or better in treatment phase 1 proceeded to treatment phase 2, when bortezomib was reduced to once weekly. Unlike in the phase III trial, PANORAMA-1 (panobinostat or placebo with bortezomib and dexamethasone in patients with relapsed multiple myeloma), bortezomib could be administered either subcutaneously or intravenously.
Thirty-nine patients with a median number of previous treatments of 4 (range, 1-12) were enrolled; most received subcutaneous bortezomib (87%). The overall response rate (partial response or better) was 56%. Grade 3/4 adverse events included thrombocytopenia (47%), fatigue (31%), dehydration (26%), and diarrhea (18%). Among the patients who received subcutaneous bortezomib, relatively low rates of peripheral neuropathy (all grade, 15%) and notable grade 3/4 adverse events (thrombocytopenia, 47%; diarrhea, 12%) were observed.
Overall, data from the PANEX trial support regulatory approval of panobinostat plus bortezomib and dexamethasone and suggest the potential tolerability benefits of subcutaneous bortezomib in this regimen.
帕比司他最近获得美国食品药品监督管理局和欧盟委员会批准，与硼替佐米及地塞米松联合用于接受过≥2种治疗方案（包括硼替佐米和一种免疫调节药物）的多发性骨髓瘤患者。PANEX（帕比司他扩展）治疗方案在帕比司他上市前提供了使用该药的机会并收集了更多安全性数据。
在治疗第1阶段，患者接受帕比司他20mg，每周3次，加硼替佐米1.3mg/m²，每周2次，在硼替佐米治疗当天及之后给予地塞米松20mg。在治疗第1阶段病情无变化或好转的患者进入治疗第2阶段，此时硼替佐米减为每周1次。与III期试验PANORAMA-1（复发多发性骨髓瘤患者中帕比司他或安慰剂联合硼替佐米及地塞米松）不同，硼替佐米可皮下或静脉给药。
入组了39例患者，既往治疗次数中位数为4次（范围1 - 12次）；大多数患者接受皮下硼替佐米治疗（87%）。总体缓解率（部分缓解或更好）为56%。3/4级不良事件包括血小板减少（47%）、疲劳（31%）、脱水（26%）和腹泻（18%）。在接受皮下硼替佐米治疗的患者中，观察到外周神经病变发生率相对较低（所有级别，15%），且3/4级不良事件发生率显著（血小板减少，47%；腹泻，12%）。
总体而言，PANEX试验数据支持帕比司他联合硼替佐米及地塞米松获得监管批准，并提示该方案中皮下注射硼替佐米可能具有耐受性优势。
