Cyclophosphamide-Bortezomib-Dexamethasone (Cybord) Compared To Bortezomib-Dexamethasone (Vel-Dex) As Induction Therapy For Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma
BLOOD(2017)
摘要
Introduction In Canada, Cyclophosphamide, bortezomib and dexamethasone (CyBorD) induction regimen has become the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM). In a phase II study, CyBorD produces a rapid and profound response without modifying the survival parameters (Leukemia . 2009 July; 23(7): 1337-1341). However, this protocol has never been compared to bortezomib and dexamethasone (Vel-Dex) regimen in a prospective trial. To compare the response at induction and at day-100 post autologous stem cell transplant (ASCT) and toxicity profiles of the Quebec population to these 2 regimens, we performed a retrospective trial in 2 tertiary centres in the Montreal area. Objectives The primary objective was to compare overall response rates and very good partial responses or better (ORR and ≥ VGPR) between CyBorD and Vel-Dex after induction and at day 100 after ASCT. The secondary objectives were the evaluation of the toxicities and the overall survival at day 100 post-ASCT. Method We performed a retrospective observational multicenter study in a cohort of patients treated in Montreal area from January 1st 2010 to June 30th 2016. The inclusion criteria were patients ≥ 18 years-old with a new symptomatic MM diagnosis defined by the 2014 International Myeloma Working Group criteria, had received a first line induction treatment with Vel-Dex or CyBorD and were transplant eligible. Continuous variables were reported as a combination of means and medians and compared using Student9s t-test and Mann-Whitney test respectively. Categorical variables were compared using Pearson9s chi-square test. Results On a total of 99 patients, 84 were included and received CyBorD (n=40) or Vel-Dex (n=44) regimen. The median age was 56 and 59 years in CyBorD and Vel-Dex group respectively. Clinical characteristics were equivalent between the two groups, except for ISS stage III MM that were more numerous in Vel-Dex group (27.3% vs 17.5%; p=0.42) and MM with del17p ≥ 10% of alleles that were more frequent in CyBorD group (12.5% vs 3.4%; p=0.41). The mean cumulative bortezomib dose was 20.6 and 24.0 mg/m2 in Vel-Dex and CyBorD group respectively (p=0.002). There were no significant differences in term of modification in the regimen schedule. ORR and ≥ VGPR rates after a median of 4 cycles of induction were 92.5% and 35% for patients treated with CyBorD, and 90.9% and 43.2% for Vel-Dex respectively (pu003e0.99 and p=0.59). At day -100 post-ASCT, an ORR and ≥ VGPR rates of 97.5% and 62.5% for the CyBorD group and 90.9% and 56.8% for the Vel-Dex group, respectively (p=0.42 and 0.76) (Fig 1). No patient died within 100 days after ASCT. Also, there was no significant difference for the number of CD34 cells mobilized (15 in Vel-Dex vs 14.7x106/kg in CyBorD group; p=0.88). Treatment options after ASCT vary between the CyBorD and Vel-Dex groups for lenalidomide maintenance (10% vs 2%; p=0.3), second ASCT (2.5% vs 20.5%; p=0.02) and allogenic mini-transplant as part of a research protocol (10% vs 0%; p=0.05). Finally, there was not any evidence of a significant difference in terms of grade 3 and 4 toxicities, except for sensitive neuropathies that were more prevalent in the Vel-Dex group (15.9% vs 0%; p=0.01) even though the cumulative dose of bortezomib was significantly lower. However the very few toxicities noted prevent us from drawing any clear conclusion. Conclusion CyBorD and Vel-Dex appear to have similar overall efficacy for newly diagnosed transplant eligible patients with MM in our cohort.Surprisingly, the response at induction and at day-100 post-ASCT in the CyBorD group did not seem better nor deeper compared to the Vel-Dex group despite more stage III MM in the latter group. At day-100 post-ASCT, there may be a trend in favour of the CyBorD group, but the sample size is too small to detect a significant difference. Adding cyclophosphamide to the chemotherapy regimen did not seem to impair the stem cell collection and was not associated with more grade 3 or 4 toxicities. Longer follow-up is required to detect if what seems to be a more favourable response post-ASCT with CyBorD leads to differences in progression free survival and overall survival. Disclosures Adam: Novartis: Honoraria; Celgene: Honoraria; Gilead: Membership on an entity9s Board of Directors or advisory committees; Takeda: Membership on an entity9s Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Honoraria; Janssen: Honoraria; Apobiologix: Honoraria. Lemieux-Blanchard: Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; BMS: Research Funding; Janssen: Research Funding.
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关键词
multiple myeloma,cybord,transplant eligible patients,cyclophosphamide-bortezomib-dexamethasone,vel-dex
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