Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p
Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p
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DOI：
10.1182/blood-2011-09-379164
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发表时间：
2012-01-26
期刊：
影响因子：
20.3
通讯作者：
Goldschmidt, Hartmut
中科院分区：
文献类型：
--
作者：
Neben, Kai;Lokhorst, Henk M.;Goldschmidt, Hartmut
在多发性骨髓瘤（MM）患者中，通过染色体异常进行风险分层可以更合理地选择治疗方法。在本研究中，我们分析了在HOVON-65/GMMG-HD4试验中治疗的354名MM患者的12个染色体异常的预后价值。由于该研究的两组设计，我们能够分析基于硼替佐米的治疗在自体干细胞移植（B组）前后与不含硼替佐米的标准治疗（a组）的效果。对于所有分析的染色体畸变，与标准组相比，硼替佐米组的无进展生存期（PFS）和总生存期（OS）至少相等或更高。引人注目的是，del（17p13）患者从含硼替佐米治疗中获益最多：A组的中位PFS为12.0个月，B组的中位PFS为26.2个月（P = 0.024）；A组3年os为17%，B组3年os为69% （P = 0.028）。经多因素分析，del（17p13）是A组PFS （P < 0.0001）和OS （P < 0.0001）的独立预测因子，而b组对PFS （P = 0.28）和OS （P = 0.12）的影响无统计学意义。综上所示，以硼替佐米为基础的治疗可显著降低del（17p13）对PFS和OS的不良影响，提示携带del（17p13）的患者应推荐长期服用硼替佐米。该试验已在国际标准随机对照试验编号登记册上注册为is - rctn64455289。（血液，2012;119(4):940-948）
In patients with multiple myeloma (MM), risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches. In the present study, we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Because of the 2-arm design of the study, we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation (arm B) compared with standard treatment without bortezomib (arm A). For all analyzed chromosomal aberrations, progression-free survival (PFS) and overall survival (OS) were at least equal or superior in the bortezomib arm compared with the standard arm. Strikingly, patients with del(17p13) benefited the most from the bortezomib-containing treatment: the median PFS in arm A was 12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A was 17% and for arm B it was 69% (P = .028). After multivariate analysis, del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in arm A, whereas no statistically significant effect on PFS (P = .28) or OS (P = .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13). This trial is registered at the International Standard Randomised Controlled Trial Number Register as IS-RCTN64455289. (Blood. 2012;119(4): 940-948)