Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Introduction : Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods : The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: Ninety-one patients have received CyBorD and 56 have received LD. Clinical characteristics are shown in Table 1 . At the time of analysis, 64 and 32 patients in the CyBorD and LD are alive of which 10 and 11, respectively, have progressed, ORR and VGPR rates were 85.7% and 56% for patients treated with CyBorD, and 83.9% and 64% for LD respectively (p=0.3). Estimated median OS was 40 months for CyBorD compared to 66 months for LD (p=0.156). In addition, median PFS was longer for LD patients compared to CyBorD (26 months vs 16.4 months, p=0.018). The rate of treatment discontinuation was similar between both groups (8.7% vs 10%, p=0.3). In Conclusion: CyBorD and LD appeared to be effective treatment options for NTE myeloma patients with similar response rates. Recognizing the limitations of a retrospective series, it is interesting to note a longer PFS and a trend towards better PFS in the LD group, however, longer follow-up and prospective validation is still required. | Characteristic | CyBorD, n=91 | LD, n=56 | P value | | ---------------------------------------------------------------------------------------- | ------------------------------------------------- | ------------------------------------------------ | ------- | | Age (median) | 73.9 | 73.6 | 0.2 | | Gender Male Female | 57 (62.6%) 34 (37.4%) | 34 (60.7%) 22 (39.3%) | 0.8 | | B2microglobulin (µmol/L) | 4.9 | 4.89 | 0.4 | | Albumin (g/L) | 35 | 36 | 0.7 | | Stage I Stage II Stage III | 17.7% 35.4% 46.9% | 23.5% 37.2% 39.3% | 0.6 | | BMPC (%) | 32 | 37.5 | 0.6 | | Heavy chain: IgG IgA FLC only IgD IgM Biclonal | 50 10 18 1 1 3 | 26 17 9 0 1 0 | 0.068 | | Response rate ORR CR/nCR VGPR PR | 85.7% 23% 31.8% 30.7 | 83.9% 28% 37.5% 17.8% | 0.3 | * Ab : BMPC: Bone marrow plasma cell Table 1. Clinical Characteristics ![Figure 1.][1] Figure 1. Overall Survival according to treatment regimen ![Figure 2.][1] Figure 2. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; JJ Celgene: Honoraria, Research Funding; Amgen: Honoraria. Sandhu: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan: Celgene: Honoraria; Jansen: Honoraria. Neri: Celgene: Research Funding. Bahlis: Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. [1]: pending:yes