Mateos María-Victoria, Bringhen Sara, Richardson Paul G, Lahuerta Juan Jose, Larocca Alessandra, Oriol Albert, Boccadoro Mario, García-Sanz Ramón, Di Raimondo Francesco, Esseltine Dixie-Lee, van de Velde Helgi, Desai Avinash, Londhe Anil, San Miguel Jesús F, Palumbo Antonio
Servicio de Hematología, Hospital Universitario de Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista, Torino, Italy.
Haematologica. 2014 Jun;99(6):1114-22. doi: 10.3324/haematol.2013.099341. Epub 2014 Apr 24.
Substantial efficacy has been demonstrated with bortezomib-melphalan-prednisone in phase III studies in transplant-ineligible myeloma patients using various twice-weekly and once-weekly bortezomib dosing schedules. In VISTA, the regimen comprised four 6-week twice-weekly cycles, plus five 6-week once-weekly cycles. In the GIMEMA MM-03-05 study, the bortezomib-melphalan-prednisone regimen was either per VISTA ('GIMEMA twice-weekly'), or comprised nine 5-week once-weekly cycles ('GIMEMA once-weekly'). In the GEM2005MAS65 study, the regimen comprised one 6-week twice-weekly cycle, plus five 5-week once-weekly cycles. We evaluated the cumulative bortezomib dose administered during bortezomib-melphalan-prednisone, as well as efficacy and tolerability, using patient-level study data. Over all bortezomib-melphalan-prednisone cycles (nine in VISTA/GIMEMA; six in GEM2005MAS65), the median cumulative bortezomib dose administered was 38.5, 42.1, 40.3, and 32.9 mg/m(2) in VISTA, GIMEMA twice-weekly, GIMEMA once-weekly, and GEM2005MAS65, respectively, and the respective proportions of planned bortezomib dose actually delivered were 57.0%, 62.3%, 86.1%, and 90.4%. Response rates following bortezomib-melphalan-prednisone were 74-87% and appeared generally similar between studies. Three-year survival rates were 67.9-75.7% across studies. Grade 3/4 peripheral neuropathy rates were 13% in VISTA and 14% in GIMEMA twice-weekly, but were lower at 2% in GIMEMA once-weekly and 7% in GEM2005MAS65. Discontinuations and bortezomib dose reductions due to peripheral neuropathy were reduced in GIMEMA once-weekly versus VISTA and GIMEMA twice-weekly. Exclusive or predominant use of once-weekly bortezomib dosing in GIMEMA once-weekly and GEM2005MAS65 resulted in high efficacy, comparable with that demonstrated in VISTA, and similar cumulative bortezomib dose with reduced toxicity. Trials are registered with ClinicalTrials.gov: VISTA (Identifier:00111319), GIMEMA MM-03-05 (Identifier:01063179), and GEM2005MAS65 (Identifier:00443235).
在针对不符合移植条件的骨髓瘤患者进行的III期研究中，使用多种每周两次和每周一次的硼替佐米给药方案，硼替佐米-美法仑-泼尼松已显示出显著疗效。在VISTA研究中，该方案包括四个为期6周的每周两次周期，外加五个为期6周的每周一次周期。在GIMEMA MM-03-0五研究中，硼替佐米-美法仑-泼尼松方案要么按照VISTA方案（“GIMEMA每周两次”），要么包括九个为期5周的每周一次周期（“GIMEMA每周一次”）。在GEM2005MAS65研究中，该方案包括一个为期6周的每周两次周期，外加五个为期5周的每周一次周期。我们使用患者层面的研究数据，评估了硼替佐米-美法仑-泼尼松治疗期间给予的累积硼替佐米剂量，以及疗效和耐受性。在所有硼替佐米-美法仑-泼尼松周期（VISTA/GIMEMA为九个；GEM2005MAS65为六个）中，VISTA、GIMEMA每周两次、GIMEMA每周一次和GEM2005MAS65中给予的硼替佐米累积剂量中位数分别为38.5、42.1、40.3和32.9mg/m²，实际给予的计划硼替佐米剂量的相应比例分别为57.０%、62.3%、86.1%和90.4%。硼替佐米-美法仑-泼尼松治疗后的缓解率为74-87%，各研究之间总体相似。各研究的三年生存率为67.9-75.7%。VISTA研究中3/4级周围神经病变发生率为13%，GIMEMA每周两次研究中为14%，但GIMEMA每周一次研究中较低，为2%，GEM2005MAS65研究中为7%。与VISTA和GIMEMA每周两次相比，GIMEMA每周一次因周围神经病变导致的停药和硼替佐米剂量减少情况有所减少。GIMEMA每周一次和GEM2005MAS65中每周一次硼替佐米给药的独家或主要使用导致了高疗效，与VISTA研究中显示的疗效相当，且累积硼替佐米剂量相似，但毒性降低。这些试验已在ClinicalTrials.gov注册：VISTA（标识符：00111319）、GIMEMA MM-03-05（标识符：01063179）和GEM2005MAS65（标识符：00443235）。
