State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China; and.
Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Blood Adv. 2019 Mar 12;3(5):751-760. doi: 10.1182/bloodadvances.2018019851.
The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [ < .001]; OS: 51, 30, 22, and 2.0 months, respectively [ < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [ = .022], respectively; OS: 41 and 58 months [ < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [ = .617], respectively; OS: 22 and 27 months [ = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.
硼替佐米为基础的蛋白酶体抑制剂（PI）治疗多发性骨髓瘤（MM）显著改善了 MM 患者的生存。26S 蛋白酶体抑制剂通过抑制泛素化副蛋白的蛋白酶体降解来靶向未折叠蛋白反应（UPR），随后导致内质网中副蛋白的致命积累。根据单克隆免疫球蛋白的分泌状态，新诊断的 MM（NDMM）分为可测量和不可测量疾病，包括寡分泌、非分泌和非产生骨髓瘤。本研究分析了 822 例接受硼替佐米或沙利度胺为基础的治疗的 NDMM 患者中可测量或不可测量疾病患者的临床特征。我们的结果表明，与寡分泌、非分泌和非产生 MM 相比，可测量疾病患者的 MM 中位无进展生存期（PFS）和总生存期（OS）明显更长（PFS：27、18、19 和 2.0 个月，分别[<0.001]；OS：51、30、22 和 2.0 个月，分别[<0.001]）。在不可测量组中，非产生骨髓瘤患者的 PFS 和 OS 最短。重要的是，与沙利度胺治疗相比，硼替佐米显著改善了可测量疾病患者的 MM 的 PFS 和 OS（PFS：25 和 33 个月，分别[=0.022]；OS：41 和 58 个月，分别[<0.001]），但对不可测量疾病患者无显著改善（PFS：18 和 16 个月，分别[=0.617]；OS：22 和 27 个月，分别[=0.743]）。我们的结果表明，硼替佐米为基础的治疗在不可测量 MM 患者中并不优于沙利度胺为基础的治疗。需要在其他患者队列中进行验证，最好在前瞻性试验中进行。
