VTD (Velcade, Thalidomide, Dexamethasone) as Primary Therapy for Newly-Diagnosed Multiple Myeloma.

Abstract

Abstract The combination of thalidomide and dexamethasone (TD) has induced disease remission in 69% of 132 newly diagnosed patients with multiple myeloma (MM) treated at our center, with preventable and/or manageable side effects, and represents our primary treatment of choice. By adding bortezomib (Velcade), the 3-drug combination (VTD) has induced remission in 55% of patients with myeloma resistant to standard therapies, twice the frequency observed with bortezomib alone (Zangari, Barlogie et al, 2003). From 6/03 to 6/04, we combined bortezomib with thalidomide (100–200 mg each evening) and dexamethasone (20 mg/m2 on days 1–4, 9–12, 17–20) with therapeutic anticoagulation for 25 previously untreated patients with MM. Bortezomib was given at a dose of 1.0 (n=2), 1.3 (n=11), 1.5 (n=7), 1.7 (n=4) or 1.9 (n=1) mg/m2 IV on days 1, 4, 8 and 11, every 4 weeks to patients for 2–3 cycles of VTD. Median age was 63 (39–81), median B2M 5.1 mg/L (1.7–19), Hgb <10.5 g/dl in 60%, corrected serum calcium >11.5 mg/dl in 17%, and high tumor mass in 32% of patients. Grade 3 or 4 toxicities included non-neutropenic infection (2), orthostatic hypotension (1), DVT (1), neutropenia (1), thrombocytopenia (1); grade 3 or 4 neuropathy was not seen. Median nadir of ANC was 2360/ul and of platelets 135,000/ul with no correlation between bortezomib dose and myelosuppression. An initial dose of bortezomib of 1.5 mg/m2 IV x 4 was safe unless age > 70 and/or drugs for hypertension were taken concurrently. Responses were confirmed (>75% reduction serum myeloma protein and/or >95% reduction Bence Jones protein) in 19 patients (76%) and when defined by less stringent Blade criteria in 21 patients (84%); median time to remission was 0.6 mo (range 0.3–1.8) by either criteria in comparison with 1.1 mo (range 0.3–8.1) after TD (p<.01). Disease resistance was recognized by one month in 5 of 6 patients rated as unresponsive. Autologous blood stem cells were collected easily with G-CSF alone in 12 patients who were intensified a median 3.6 months after initial therapy; all 4 patients with primary resistant disease who received such therapy achieved partial remission. The frequency of CR to VTD could not be assessed because of early intensification. All patients are alive after median follow-up of 6 months (range 2–14). VTD induced a slightly higher frequency of PR, and significantly more rapid onset of remission, than those observed in similar patients treated previously with TD. No more than 2 courses of therapy were necessary before intensification or maintenance, so that the potential side effects and cost of more therapy were avoided. Results appeared superior to those observed with any prior program for previously untreated patients with MM at our center.