Haematology Department, Hospital Morales Meseguer, Murcia, Spain.
Haematology Department, Hospital General de Jaén, Jaén, Spain.
Semin Hematol. 2018 Oct;55(4):189-196. doi: 10.1053/j.seminhematol.2017.09.002. Epub 2017 Oct 13.
Bortezomib-melphalan-prednisone combination is one of the standards of care for nontransplant eligible patients with newly diagnosed multiple myeloma. However, bortezomib intravenous (twice weekly for 4 cycles then weekly for 5 cycles) results in ~13% of patients with grade 3-4 peripheral neuropathy. Bortezomib subcutaneous (SQ) and weekly delivery, improves tolerability without impairment of efficacy. The aim of this study was to evaluate the safety and effectiveness of SQ bortezomib-based combinations in nontransplant eligible patients with newly diagnosed myeloma in a real-world setting. A total of 135 patients (median age [range] = 76 [58-89], International Staging System-III = 54%, median follow-up = 14.8 months [1-40], Intensive group [twice weekly bortezomib] = 65%, Optimized group [weekly bortezomib] = 35%) were included and evaluable for safety, whereas 121 were evaluable for effectiveness. Overall response rate (95% CI) was 61% (53%, 71%) (complete response = 27%, very good partial response = 13%, and partial response = 21%) and median progression-free survival was 22.2 months (95% CI: 16.1-not reached). The 3-year overall survival was 75%. The most frequent grade 3-4 adverse events were thrombocytopenia (18%), neutropenia (17%), and anemia (11%). Peripheral neuropathy of any grade was observed in 44% of patients (2% with grade 3). Comparison between regimens (Intensive vs Optimized) showed similar overall response rate (57% vs 70%) and PFS (25 vs 19 months). A similar safety profile was observed between regimens. Thus, SQ bortezomib showed similar effectiveness and better tolerability as compared with results from intravenous bortezomib studies, and showing no differences either in effectiveness or safety in different bortezomib-based combinations.
硼替佐米-美法仑-泼尼松联合方案是新诊断多发性骨髓瘤不适合移植患者的标准治疗方法之一。然而，静脉注射硼替佐米（每两周 4 个周期，然后每周 5 个周期）导致约 13%的患者出现 3-4 级周围神经病变。皮下注射硼替佐米（SQ）和每周给药可提高耐受性而不影响疗效。本研究旨在评估在真实环境中，新诊断骨髓瘤不适合移植的患者使用 SQ 硼替佐米为基础的联合方案的安全性和有效性。共纳入 135 例患者（中位年龄[范围]为 76[58-89]岁，国际分期系统-III 期=54%，中位随访时间为 14.8 个月[1-40]，强化组[每周两次硼替佐米]为 65%，优化组[每周硼替佐米]为 35%），其中 135 例可评估安全性，121 例可评估有效性。总体缓解率（95%CI）为 61%（53%，71%）（完全缓解=27%，非常好的部分缓解=13%，部分缓解=21%），中位无进展生存期为 22.2 个月（95%CI：16.1-未达到）。3 年总生存率为 75%。最常见的 3-4 级不良事件是血小板减少症（18%）、中性粒细胞减少症（17%）和贫血（11%）。任何等级的周围神经病变在 44%的患者中观察到（3 级为 2%）。方案间比较（强化组与优化组）显示总缓解率（57% vs 70%）和 PFS（25 个月 vs 19 个月）相似。两种方案的安全性相似。因此，与静脉注射硼替佐米研究相比，SQ 硼替佐米显示出相似的疗效和更好的耐受性，并且在不同的硼替佐米为基础的联合方案中，无论是在疗效还是安全性方面均无差异。
