Pieter Sonneveld, Erasmus Medical Center, Rotterdam; Henk M. Lokhorst, Utrecht Medical Center, Utrecht, the Netherlands; Hartmut Goldschmidt, University Hospital of Heidelberg, Heidelberg, Germany; Laura Rosiñol, Joan Bladé, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona; Juan José Lahuerta, Hospital Universitario 12 de Octubre, Madrid, Spain; Michele Cavo, Paola Tacchetti, Elena Zamagni, Istituto di Ematologia Seràgnoli, Università degli Studi di Bologna, Bologna, Italy; Michel Attal, Hopital Purpan, Toulouse; Philippe Moreau, University Hospital, Nantes, France; Avinash Desai, Janssen Global Services; Kevin Liu, Janssen Research and Development, Raritan, NJ; Dixie-Lee Esseltine, Millennium Pharmaceuticals, Cambridge, MA; Andrew Cakana, Janssen Research and Development, High Wycombe, United Kingdom; Helgi van de Velde, Janssen Research and Development, Beerse, Belgium.
J Clin Oncol. 2013 Sep 10;31(26):3279-87. doi: 10.1200/JCO.2012.48.4626. Epub 2013 Jul 29.
PURPOSE: To characterize efficacy and safety of bortezomib-based versus nonbortezomib-based induction regimens through an integrated analysis of data from phase III studies in transplantation-eligible patients with previously untreated myeloma. PATIENTS AND METHODS: Patient-level data from the IFM 2005-01 (bortezomib-dexamethasone v vincristine-doxorubicin-dexamethasone [VAD] induction), HOVON-65/GMMG-HD4 (bortezomib-doxorubicin-dexamethasone v VAD), and PETHEMA GEM05MENOS65 (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) studies were pooled in an integrated analysis of efficacy and safety. Study-level data from the GIMEMA MM-BO2005 study (bortezomib-thalidomide-dexamethasone v thalidomide-dexamethasone) supplemented the integrated patient-level analysis. Key efficacy end points were post-transplantation complete plus near-complete response (CR+nCR) rate and progression-free survival (PFS). RESULTS: Patient-level data for 1,572 patients (bortezomib-based induction, n = 787; nonbortezomib-based induction, n = 785) were included. Post-transplantation CR+nCR rate was significantly higher following bortezomib-based versus nonbortezomib-based induction (38% v 24%; odds ratio, 2.05; P < .001); the benefit remained similar (pooled odds ratio, 1.96) when GIMEMA MM-BO2005 data were included. Median PFS was 35.9 months versus 28.6 months with bortezomib-based versus nonbortezomib-based induction, respectively (hazard ratio, 0.75; P < .001); 3-year overall survival (OS) rates were 79.7% and 74.7%, respectively (hazard ratio for OS, 0.81; P = .0402). Median duration of induction treatment was 11 weeks in both treatment groups. Rates of peripheral neuropathy during induction were 34% versus 17% (grade ≥ 3, 6% v 1%). Overall, 3% and 4% of patients died during bortezomib-based and nonbortezomib-based induction, respectively. CONCLUSION: Bortezomib-based induction results in significant improvements in response and PFS/OS compared with nonbortezomib-based induction and is generally well tolerated, with a higher rate of peripheral neuropathy but no apparent increase in risk of death during induction.
目的：通过对先前未经治疗的多发性骨髓瘤移植合格患者的 III 期研究数据进行综合分析，描述基于硼替佐米和非硼替佐米诱导方案的疗效和安全性。
方法：对 IFM 2005-01（硼替佐米-地塞米松 v 长春新碱-多柔比星-地塞米松[VAD]诱导）、HOVON-65/GMMG-HD4（硼替佐米-多柔比星-地塞米松 v VAD）和 PETHEMA GEM05MENOS65（硼替佐米-沙利度胺-地塞米松 v 沙利度胺-地塞米松）研究的患者水平数据进行汇总分析，以评估疗效和安全性。GIMEMA MM-BO2005 研究（硼替佐米-沙利度胺-地塞米松 v 沙利度胺-地塞米松）的研究水平数据补充了综合患者水平分析。主要疗效终点为移植后完全缓解+接近完全缓解（CR+nCR）率和无进展生存期（PFS）。
结果：纳入了 1572 例患者（硼替佐米组 n = 787，非硼替佐米组 n = 785）的患者水平数据。与非硼替佐米组相比，硼替佐米组的移植后 CR+nCR 率显著提高（38% v 24%；比值比，2.05；P<0.001）；当纳入 GIMEMA MM-BO2005 数据时，该获益仍相似（合并比值比，1.96）。硼替佐米组和非硼替佐米组的中位 PFS 分别为 35.9 个月和 28.6 个月（风险比，0.75；P<0.001）；3 年总生存率（OS）分别为 79.7%和 74.7%（OS 的风险比，0.81；P = 0.0402）。两组诱导治疗的中位持续时间均为 11 周。诱导期间周围神经病的发生率分别为 34%和 17%（≥3 级，6% v 1%）。总体而言，硼替佐米组和非硼替佐米组分别有 3%和 4%的患者在诱导期间死亡。
结论：与非硼替佐米诱导相比，硼替佐米诱导可显著提高缓解率和 PFS/OS，且耐受性良好，周围神经病发生率较高，但诱导期间死亡风险无明显增加。
Cancers (Basel). 2023-7-20
Curr Hematol Malig Rep. 2023-10
Zotero 插件