Superiority of Triple Combination Bortezomib + Cyclophosphamide and Dexamethasone (VCD) Versus Thalidomide + Cyclophosphamide and Dexamethasone (CTD) in Newly Diagnosed Multiple Myeloma Transplant-Eligible Patients

Background- The treatment of multiple myeloma has evolved significantly in the last decade and combinations of the new drugs have allowed better responses and significant gain in survival. Studies comparing different chemotherapy combinations before transplant suggest that the triple combo is superior to double. The use of bortezomib as backbone in these combos has been identified as superior to other drugs. Unfortunately bortezomib is not part of the drugs available for use in the Brazilian public health system to myeloma treatment and the only available drug is thalidomide. Comparisons between different triple combinations are rare in the literature. In the present study we compared two different triple combinations composed of bortezomib + cyclophosphamide + dexamethasone (VCD) versus thalidomide + cyclophosphamide + dexamethasone (CTD) in order to identify which of the two combinations lead to the best response after 4 cycles before bone marrow transplantation for eligible new diagnose patients with multiple myeloma.

Methods- The patients that were submitted to induction treatment with VCD or CTD protocol between June 2009 and June 2014 had been included retrospectively from 24 different centers. The primary endpoint was very good partial response (VGPR) rate or better following 4 cycles. Response was re-assessed in a central evaluation according to the IMWG criteria.

Results- A total of 311 patients were included from 24 centers, of which eight are private and the others 16 were public/philanthropic. The VCD combination was used as induction by 117 (37.6%) patients, and 194 (62.4%) patients performed the CTD scheme. After four cycles of induction, we identified as a intention to treat base that better than very good partial response was 54% for the VCD group versus 42.8% for the CTD group (p = 0.05). Regarding toxicity two alterations were evaluated: Neuropathy was reported in 114 cases, 46 in the VCD group (39.3%) and 68 in the CTD group (35.1%) and grade > 3 of neuropathy represent 10% and 7% respectively. There was no statistically difference between the two groups (p = 0.526). And thrombosis was reported in only 14 cases (four patients treated with VCD and 10 with CTD), without significant difference.

Conclusion- This is the first multicentric analysis between two main treatments used in Brazilian centers as induction for eligible multiple myeloma patients. VCD showed significant superiority to CTD in terms of VGPR or better. Neuropathy rates low in both groups. Our finds reinforce the need to make bortezomib available as a treatment option for all patients with multiple myeloma in Brazil.