Uttervall Katarina, Duru Adil D, Lund Johan, Liwing Johan, Gahrton Gösta, Holmberg Erik, Aschan Johan, Alici Evren, Nahi Hareth
Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden; Hematology Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden.
PLoS One. 2014 Jul 8;9(7):e101819. doi: 10.1371/journal.pone.0101819. eCollection 2014.
Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor.
To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response.
The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2.
The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients.
High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.
肾功能损害是多发性骨髓瘤的常见特征,被认为是一个不良预后因素。
确定新型药物(即硼替佐米、来那度胺和沙利度胺)对肾功能损害的骨髓瘤患者治疗的影响。主要终点是总生存期,次要终点是下次治疗时间和缓解情况。
研究人群包括2000年1月至2011年6月在15家瑞典医院诊断为需要治疗的多发性骨髓瘤的所有患者。肾功能损害定义为估计肾小球滤过率低于60 mL/分钟/1.73平方米。
研究人群包括1538例患者,其中680例在诊断时存在肾功能损害。肾功能损害患者的中位总生存期为33个月,明显短于肾功能正常患者的52个月(P<0.001)。与接受传统细胞毒性药物治疗的患者(n = 411,中位生存期27个月)相比,一线使用新型药物可改善未接受高剂量治疗的肾功能损害患者(n = 143)的总生存期(中位生存期60个月)(P<0.001)。在多变量分析中,硼替佐米的前期治疗是未接受高剂量治疗的肾功能损害患者总生存期较好的独立因素。接受高剂量治疗的肾功能损害患者的中位总生存期明显优于未接受高剂量治疗的患者(74个月对26个月),新型药物在这些患者中并未进一步显著改善生存期。与肾功能正常的患者相比,肾功能损害患者的下次治疗中位时间较短,缓解率较低。然而,新型药物和高剂量治疗可使下次治疗时间显著延长,新型药物显著提高了这些患者的缓解率。
高剂量治疗和新型药物,尤其是硼替佐米,可有效克服肾功能损害对多发性骨髓瘤患者的负面影响。