文章：

奈非那韦联合来那度胺/地塞米松治疗来那度胺难治性多发性骨髓瘤患者：一项I/II期试验（SAKK 39/10）

Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10)

原文发布日期：2019-08-27

DOI: 10.1038/s41408-019-0228-2

类型: Article

开放获取: 是

英文摘要：

The antiretroviral agent nelfinavir has antimyeloma activity and can overcome resistance to bortezomib. Our phase I/II trial investigated whether adding nelfinavir to lenalidomide–dexamethasone can overcome lenalidomide resistance in lenalidomide-refractory multiple myeloma (MM). Twenty-nine patients were included (high-risk cytogenetic aberrations 31%; ≥2 prior therapy lines 93%; lenalidomide–bortezomib double-refractory 34%). Twenty-four patients (83%) had prior bortezomib and 10 (34%) were lenalidomide–bortezomib double-refractory. They received four cycles of nelfinavir 2500 mg/day with standard-dose lenalidomide (25 mg days 1–21) and dexamethasone (40/20 mg days 1, 8, 15, 22). Minor response or better was achieved in 16 patients (55%; 95% CI 36–74%), including 40% of those who were lenalidomide–bortezomib double-refractory, and partial response or better in nine patients (31%; 95% CI 15–51%). Median progression-free survival was 3.4 (95% CI 2.0–4.9) months and median overall survival 21.6 (13.0–50.1) months. Lenalidomide-related pneumonitis, pneumonia, and neutropenic fever occurred, but there were no unexpected adverse events. Peripheral blood mononuclear cells showed a 45% (95% CI 40–51%) reduction in total proteasome activity from baseline and significant induction of unfolded protein response and autophagy. Thus, nelfinavir–lenalidomide–dexamethasone is an active oral combination in lenalidomide-refractory MM.
 

摘要翻译： 

抗逆转录病毒药物奈非那韦具有抗骨髓瘤活性，且能克服对硼替佐米的耐药性。我们的I/II期临床试验研究了在来那度胺-地塞米松方案中加入奈非那韦能否克服来那度胺耐药型多发性骨髓瘤（MM）患者的来那度胺耐药。研究共纳入29例患者（高危细胞遗传学异常占31%；既往接受≥2线治疗占93%；来那度胺-硼替佐米双重耐药占34%）。其中24例（83%）曾接受硼替佐米治疗，10例（34%）为来那度胺-硼替佐米双重耐药患者。患者接受为期4周期的奈非那韦（2500毫克/日）联合标准剂量来那度胺（第1-21日每日25毫克）及地塞米松（第1、8、15、22日每日40/20毫克）治疗。16例患者达到轻微缓解及以上疗效（55%；95%CI 36-74%），其中包括40%的双重耐药患者；9例达到部分缓解及以上（31%；95%CI 15-51%）。中位无进展生存期为3.4个月（95%CI 2.0-4.9），中位总生存期为21.6个月（95%CI 13.0-50.1）。虽出现来那度胺相关间质性肺炎、肺炎及中性粒细胞减少性发热，但未发生非预期不良事件。外周血单核细胞显示总蛋白酶体活性较基线下降45%（95%CI 40-51%），并显著诱导未折叠蛋白反应及自噬。结果表明，奈非那韦-来那度胺-地塞米松是治疗来那度胺耐药型多发性骨髓瘤的有效口服联合方案。

原文链接：

Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10)