The Clinical Impact and Molecular Biology of del(17p) in Multiple Myeloma Treated with Conventional or Thalidomide-Based Therapy
The Clinical Impact and Molecular Biology of del(17p) in Multiple Myeloma Treated with Conventional or Thalidomide-Based Therapy
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DOI：
10.1002/gcc.20899
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发表时间：
2011-10-01
影响因子：
3.7
通讯作者：
Morgan, Gareth J.
中科院分区：
文献类型：
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作者：
Boyd, Kevin D.;Ross, Fiona M.;Morgan, Gareth J.
17p 的半合子缺失 (del(17p)) 已被确定为与骨髓瘤预后不良相关的一个变量，尽管其在沙利度胺治疗背景下的影响尚未得到很好的描述。在一项结合传统疗法和基于沙利度胺的诱导疗法的临床试验中，对 85 名 del(17p) 骨髓瘤患者的临床结果进行了检查。还确定了 TP53 缺失、低表达和突变的临床影响。与不具有 del(17p) 的患者相比，具有 del(17p) 的患者的缓解率并不差，但尽管如此，del(17p) 仍与总生存期 (OS) 受损相关（中位 OS 26.6 个月与 48.5 个月，P < 0.001）。在 del(17p) 组中，与传统疗法相比，沙利度胺诱导疗法可提高缓解率，但对 OS 没有影响。沙利度胺维持治疗与 OS 受损相关，尽管我们的分析表明这种影响可能是由于混杂变量造成的。鉴定出 17p13.1 上涉及 17 个基因的最小缺失区域，其中仅 TP53 和 SAT2 表达不足。在没有 del(17p) 的患者中，TP53 的突变率 < 1%，在有 del(17p) 的患者中，TP53 的突变率为 27%。 del(17p) 样本中较高的 TP53 突变率表明 TP53 在这些临床结果中发挥作用。总之，del(17p) 定义了与骨髓瘤生存期短相关的患者组，尽管沙利度胺诱导治疗与改善反应率相关，但它并不影响 OS，表明该组需要替代治疗策略。 (C) 2011 Wiley-Liss, Inc.
Hemizygous deletion of 17p (del(17p)) has been identified as a variable associated with poor prognosis in myeloma, although its impact in the context of thalidomide therapy is not well described. The clinical outcome of 85 myeloma patients with del(17p) treated in a clinical trial incorporating both conventional and thalidomide-based induction therapies was examined. The clinical impact of deletion, low expression, and mutation of TP53 was also determined. Patients with del(17p) did not have inferior response rates compared to patients without del(17p), but, despite this, del(17p) was associated with impaired overall survival (OS) (median OS 26.6 vs. 48.5 months, P < 0.001). Within the del(17p) group, thalidomide induction therapy was associated with improved response rates compared to conventional therapy, but there was no impact on OS. Thalidomide maintenance was associated with impaired OS, although our analysis suggests that this effect may have been due to confounding variables. A minimally deleted region on 17p13.1 involving 17 genes was identified, of which only TP53 and SAT2 were underexpressed. TP53 was mutated in < 1% in patients without del(17p) and in 27% of patients with del(17p). The higher TP53 mutation rate in samples with del(17p) suggests a role for TP53 in these clinical outcomes. In conclusion, del(17p) defined a patient group associated with short survival in myeloma, and although thalidomide induction therapy was associated with improved response rates, it did not impact OS, suggesting that alternative therapeutic strategies are required for this group. (C) 2011 Wiley-Liss, Inc.