文章：

帕比司他、来那度胺、硼替佐米联合地塞米松治疗复发及复发/难治性多发性骨髓瘤的I期开放标签研究

Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma

原文发布日期：2021-02-05

DOI: 10.1038/s41408-021-00407-5

类型: Article

开放获取: 是

英文摘要：

Additional therapeutic options are needed for relapsed and refractory multiple myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 50–77]) and a median of four prior regimens (range: 2–14); 85% had refractory disease (lenalidomide [80%]; bortezomib [75%]; lenalidomide and bortezomib [50%]). Patients received a median of six cycles (range: 1–74) of panobinostat (10 or 15 mg), lenalidomide 15 mg, bortezomib 1 mg/m2, and dexamethasone 20 mg (pano-RVd). Median follow-up was ~14 months. Six dose-limiting toxicities were reported (mostly hematological); maximum tolerated dose of panobinostat (primary endpoint) was 10 mg. Most common adverse events (AEs) were diarrhea (60%) and peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of patients and included decreased neutrophil (45%), platelet (25%) and white blood cell (25%) counts, anemia (25%) and hypophosphatemia (25%). No treatment-related discontinuations or mortality occurred. In evaluable patients (n = 18), overall response rate was 44%, and clinical benefit rate was 61%. Median duration of response was 9.2 months; progression-free survival was 7.4 months; overall survival was not reached. Pano-RVd proved generally well-tolerated and demonstrated potential to overcome lenalidomide and/or bortezomib resistance.
 

摘要翻译： 

复发难治性多发性骨髓瘤（RRMM）需要更多的治疗选择。本研究报道了一项Ib期、开放标签、剂量递增试验（NCT01965353）的数据，该试验纳入了20例RRMM患者（中位年龄63岁[范围：50-77]），既往中位治疗线数为4线（范围：2-14）；85%为难治性患者（对来那度胺[80%]、硼替佐米[75%]、来那度胺联合硼替佐米[50%]耐药）。患者接受了中位6个周期（范围：1-74）的帕比司他（10或15mg）、来那度胺15mg、硼替佐米1mg/m²及地塞米松20mg（pano-RVd方案）治疗。中位随访时间约为14个月。报告了6例剂量限制性毒性（主要为血液学毒性）；帕比司他的最大耐受剂量（主要终点）为10mg。最常见的不良事件是腹泻（60%）和周围神经病变（60%），均为1/2级。80%的患者出现3/4级不良事件，包括中性粒细胞减少（45%）、血小板减少（25%）、白细胞减少（25%）、贫血（25%）和低磷血症（25%）。未发生治疗相关停药或死亡。在可评估患者（n=18）中，总体缓解率为44%，临床获益率为61%。中位缓解持续时间为9.2个月；无进展生存期为7.4个月；总生存期未达到。Pano-RVd方案总体耐受性良好，并显示出克服来那度胺和/或硼替佐米耐药的潜力。

原文链接：

Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma