Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma
Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma
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DOI：
10.1002/ajh.24107
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发表时间：
2015-10-01
影响因子：
12.8
通讯作者：
Kumar, Shaji K.
中科院分区：
文献类型：
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作者：
Binder, Moritz;Rajkumar, S. Vincent;Kumar, Shaji K.
对新诊断的症状性多发性骨髓瘤（NDMM）的治疗反应可以影响长期预后。目前尚不清楚基线实验室参数是否可以预测早期的深度反应。2001年至2013年期间，在罗切斯特梅奥诊所共有1304名NDMM患者接受了研究。研究了基线实验室参数与早期深度反应之间的关系，深度反应被定义为四个治疗周期内非常好的部分反应或更好（VGPR+）。使用多变量逻辑回归来评估感兴趣参数与反应之间的关联。采用多变量比例风险回归来评估反应与总生存率之间的关系。在整个队列中，较大的绝对游离轻链（FLC）差异（OR 2.38, 95% CI 1.48-3.82）、较年轻（OR 2.18, 95% CI 1.28-3.71）、较低的血红蛋白（OR 1.68, 95% CI 1.12-2.54）和IgA骨髓瘤（OR 1.66, 95% CI 1.10-2.51）与四个周期后实现VGPR+的几率增加相关。在接受新药治疗的患者中，尤其是免疫调节剂，这些效果更为明显。在接受蛋白酶体抑制剂治疗的患者中，较高的肌酐（OR 3.83, 95% CI 1.37-10.1）、较低的钙（OR 3.37, 95% CI 1.36-8.35）和较大的绝对FLC差异（OR 2.50, 95% CI 1.10-5.71）与较好的疗效相关。在诊断后4个月的里程碑式分析中，实现VGPR+与随后死亡风险降低相关（HR 0.69, 95% CI 0.53-0.86）。总之，几个参数与治疗的早期深度反应相关，揭示了免疫调节剂和含蛋白酶体抑制剂方案的不同预测因素。在四个周期后达到VGPR+转化为总生存期的增加。(C) 2015 Wiley期刊公司
Response to therapy in newly diagnosed symptomatic multiple myeloma (NDMM) can impact long-term outcomes. It is not clear if baseline laboratory parameters can predict an early, deep response. Totally 1,304 patients with NDMM seen between 2001 and 2013 at Mayo Clinic Rochester were studied. The association between baseline laboratory parameters and early, deep response defined as a very good partial response or better (VGPR+) within four cycles of treatment was investigated. Multivariable logistic regression was used to assess the associations between the parameters of interest and response. Multivariable proportional hazards regression was used to assess the association between response and overall survival. In the entire cohort, greater absolute free light chain (FLC) differences (OR 2.38, 95% CI 1.48-3.82), younger age (OR 2.18, 95% CI 1.28-3.71), lower hemoglobin (OR 1.68, 95% CI 1.12-2.54), and IgA myeloma (OR 1.66, 95% CI 1.10-2.51) were associated with increased odds of achieving VGPR+ after four cycles. Among patients receiving novel agents in general and immunomodulators in particular, these effects were more pronounced. In patients receiving proteasome-inhibitors, higher creatinine (OR 3.83, 95% CI 1.37-10.1), lower calcium (OR 3.37, 95% CI 1.36-8.35), and greater absolute FLC differences (OR 2.50, 95% CI 1.10-5.71) were associated with better response. In a landmark analysis at 4 months from diagnosis, achieving VGPR+ was associated with decreased risk of subsequent mortality (HR 0.69, 95% CI 0.53-0.86). In summary, several parameters were associated with an early, deep response to treatment, revealing distinct sets of predictors for immunomodulator- and proteasome-inhibitor-containing regimens. Achieving VGPR+ after four cycles translated into increased overall survival. (C) 2015 Wiley Periodicals, Inc.