Intensive sequential therapy for VAD-resistant multiple myeloma

Few effective regimens are available for patients with advanced multiple myeloma resistant to alkylating agents and VAD. We treated 65 patients with advanced and refractory multiple myeloma with the combination of cyclophosphamide (3.0 gm/m2) and etoposide (900 mg/m2) followed by GM-CSF at a daily dose of 0.125 mg/m2. Thirty-five percent of patients responded with a 6% mortality rate. After a median of 2 months, 16 patients received myeloablative treatment supported by autologous bone marrow or blood stem cells. Four of ten previously resistant patients responded so that the overall response rate was 42%. The median survival for all patients was 10 months and the median remission was 8 months. The median survival for patients with both low serum lactate dehydrogenase and B2 microglobulin, or for those who received myeloablative treatment, was projected at 18 months. Our combination of cyclophosphamide and etoposide provided an effective rescue treatment for many patients with advanced multiple myeloma resistant to conventional therapies. This program allowed early blood stem cell collection in support of subsequent myeloablative therapy for selected patients.