San-Miguel J F, Richardson P G, Sonneveld P, Schuster M W, Irwin D, Stadtmauer E A, Facon T, Harousseau J-L, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Bladé J, Boccadoro M, Cavenagh J D, Neuwirth R, Boral A L, Esseltine D-L, Anderson K C
Department of Hematology, Hospital Universitario. CIC Universidad de Salamanca-CSIC, Salamanca, Spain.
Leukemia. 2008 Apr;22(4):842-9. doi: 10.1038/sj.leu.2405087. Epub 2008 Jan 17.
Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) <30, 30-50, 51-80 and >80 ml min(-1)). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl < or =50 ml min(-1) (severe-to-moderate) and >50 ml min(-1) (no/mild impairment). Response rates with bortezomib were similar (36-47%) and time to response rapid (0.7-1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl < or =50 vs >50 ml min(-1) (P=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl < or =50 vs >50 ml min(-1). These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.
肾功能损害与多发性骨髓瘤（MM）的不良预后相关。这项对硼替佐米与高剂量地塞米松进行的3期蛋白酶体抑制延长缓解期评估（APEX）研究的亚组分析，评估了不同程度肾功能损害（肌酐清除率（CrCl）<30、30 - 50、51 - 80和>80 ml/min）的复发MM患者的疗效和安全性。比较了CrCl≤50 ml/min（中重度）和>50 ml/min（无/轻度损害）亚组之间的疾病进展时间（TTP）、总生存期（OS）和安全性。各亚组中硼替佐米的缓解率相似（36 - 47%），且缓解时间较快（0.7 - 1.6个月）。尽管中重度肾功能损害的硼替佐米患者与无/轻度损害患者相比有TTP/OS缩短的趋势，但差异不显著。CrCl≤50与>50 ml/min的地塞米松患者相比，OS显著缩短（P = 0.003），表明硼替佐米在克服肾功能损害的有害影响方面比地塞米松更有效。硼替佐米的安全性在各亚组之间具有可比性。使用地塞米松时，CrCl≤50与>50 ml/min的患者相比，3/4级不良事件（AE）、严重AE和因AE停药的情况显著增加。这些结果表明，硼替佐米在不同程度肾功能不全的复发MM患者中具有活性且耐受性良好。中重度与无/轻度损害对疗效/安全性没有实质性影响。
