Modified Thalidomide, Cyclophosphamide and Dexamethasone (TCD) to Patients with Multiple Myeloma as Primary Therapy Prior to Peripheral Blood Stem Cell Collection.

In the treatment of multiple myeloma (MM), autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy, especially for younger patients. Before PBSC, a new immunomodulatory drug, thalidomide, has replaced VAD regimen as the induction therapy of choice prior to hematopoietic stem cell procurement. Thalidomide has alternative mechanisms of action and usually combines with dexamethasone or alkylating agent, but the optimal doses and the intervals of chemotherapy has been evaluated. We reported preliminary data that the patients with previously untreated multiple myeloma were treated by combined different dose-scheduled thalidomide, cyclophosphamide, and dexamethasone as primary therapy and performed autologous stem cell collection. A total of 52 patients with MM were initially treated thalidomide-based chemotherapy from June 2003. Thalidomide was given with the three different method: 400mg/day on D1–5, D15–19 (arm A), 50mg/day daily (arm B) combined with cyclophosphamide 150mg/m² P.O. on D1–4 and dexamethasone 20mg/m² P.O. or I.V. on D1–5, D15–19, or thalidomide 200mg/day daily combined with dexamethasone 20mg/m² on D1–4, 9–12, 17–20 in odd cycles and on D1–4 in even cycles (arm C), repeated every 28 days. Low-dose aspirin or warfarin was taken as prophylaxis for thrombosis. Thirty-nine (arm A: 17, arm B: 12, arm C: 10) of the 52 patients who received at least 4 cycles or more were evaluated for response and toxicity. Median age was 65 (range: 39–80) years and the total number of 158 cycles of toxicities were evaluated. After median 4 months of time to response followed, the overall response rate was 71.8% (76.5% v 75.0% v 60.0%), including 23% (17.5% v 23% v 28%) of complete or near complete response. Two patients (5.1%) died due to infection during treatment. When the toxicity of therapy was evaluated with more Grade III, two patients (5.1%) showed neurotoxicity, six patients (15.4%) showed neutropenia, and two patients (5.1%) had deep-vein thrombosis. Thirteen patients who achieved more than partial response proceeded to PBSC collection and yielded a median number of 3.78 x 10⁶ CD 34+ cells/kg. This low or intermediate dose or periodic thalidomide combination showed positive responses, reducing toxicities, and adequate numbers of blood stem cells in patients eligible for subsequent high-dose chemotherapy.