Alternative Dosing of Cyclophosphamide, Bortezomib and Corticosteroids (CyBorD) for Relapsed/Refractory Multiple Myeloma

Abstract

5142 Background: The combination of an alkylating agent and bortezomib has been shown to be synergistic both preclinically and in the clinical arena. Although the combination of cyclophosphamide, bortezomib and corticosteroids (CyBorD) has been evaluated by several investigators, many have used different doses and schedule of cyclophosphamide and an optimal schedule has not been established. Herein, we report the safety and efficacy of this combination in patients with relapsed and refractory multiple myeloma. Methods: All patients with myeloma that received this schedule of CyBorD at the Moffitt Cancer Center were included. CyBorD was comprised of cyclophosphamide 1000 mg/2 IV on Day 1, Bortezomib 1.3 mg/m2 IV on Days 1, 4, 8, and 11 and either low dose dexamethasone (equivalent of 120– 160mg/cycle) or prednisone (100 mg PO day 1–5). Demographic, laboratory and clinical data was collected and evaluated via descriptive statistics. Response and progression are defined as per the IMWG uniform response criteria. Results: A total of 20 patients were identified and included for analysis. Demographic data is shown in table 1. At baseline, 35% of patients were platelet transfusion dependent, and the median ß2m was 6.2mg/L. 8 patients (40%) received prophylactic GCSF and 9 patients (45%) received secondary GCSF after significant neutropenia was noted. Overall response rate (PR and better) was 50% (70% minimal response and better), including 1 complete response (CR) and 5 very good partial response (VGPR). Median progression free survival was 3.4 months (95% CI 0–7.5 months) and median overall survival was 11.9 months (95% CI 3.3–20.0). The incidence of grade 3/4 neutropenia and thrombocytopenia was 80% and 75%, respectively. Grade 2 and 3 peripheral neuropahty developed in 1 and 1 patient respectively. Nine patients required dose reductions of cyclophosphamide (only 2 of the 8 who received prophylactic GCSF therapy) and 3 patients required dose reductions of the bortezomib. Conclusion: In this cohort of patients with high burden of disease, intermediate dose cyclophosphamide administered once every 3 weeks in combination with standard dose and schedule of bortezomib results in a meaningful response rate (albeit short PFS) with mainly hematologic toxicities that are manageable with growth factor support. Disclosures: Off Label Use: Cyclophosphamide in combination with bortezomib for relapsed/refractory multiple myeloma. Finley-Oliver:Millenium: Speakers Bureau. Alsina:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allergan: Research Funding. Djulbegovic:Millenium: Research Funding. Baz:Millenium: Research Funding, Speakers Bureau; Celgene: Research Funding.

An open‐label phase I/II study of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed myeloma

“…The addition of cyclophosphamide to the already established VDD regimen resulted in a similar overall response rate, but a higher VGPR or better rate. Although the dose of cyclophosphamide can be increased up to 1000 mg/m 2 intravenously every 3 wk in a combination regimen of cyclophosphamide, bortezomib, and dexamethasone (i.e., CyBorD) , we used 750 mg/m 2 of cyclophosphamide in CVDD regimen due to the addition of liposomal doxorubicin (i.e., quadruple regimen). Although comparisons across various phase 2 studies will need to be performed cautiously, multiple other combination regimens have shown similar response rates and PFS estimates at 2 yr as summarized in Table .…”