Sequential vincristine, adriamycin, dexamethasone (VAD) followed by bortezomib, thalidomide, dexamethasone (VTD) as induction, followed by high-dose therapy with autologous stem cell transplant and consolidation therapy with bortezomib for newly diagnosed multiple myeloma: results of a phase II trial

Incorporation of novel agents has resulted in an improved response rate and reduced side effects in multiple myeloma. This has prompted combining novel agents in induction chemotherapy in patients with newly diagnosed multiple myeloma. Our patients received 2 cycles of vincristine, adriamycin, dexamethasone (VAD) and then 2 cycles of bortezomib, thalidomide, dexamethasone (VTD) chemotherapy as an induction treatment. Subsequently, autologous stem cell transplantation was performed, and bortezomib was administered as a consolidation therapy. Seventy-one patients were enrolled, and 65 were evaluable for response. After 2 cycles of VAD, the overall response rate was 69%. After VTD, the response rate improved to 97% with a complete response (CR) and near CR rate of 27%. Importantly, patients with cytogenetics, having poor prognostic features, all responded after VTD. Autologous stem cells were successfully collected in all 58 patients with a median CD34+ cell count of 7.12 x 10(6)/kg (range, 1.94-44.7 x 10(6)/kg), except in 1 patient (2%). After ASCT, 36 patients completed bortezomib maintenance with a combined CR and near CR rate approaching 75%. Median time to response was rapid (1.6 months). With a median follow-up duration of 52.7 months, the median TTP was 29.4 months and median OS was not reached. Toxicities proved manageable. In conclusion, sequential VAD and VTD induction therapy in patients with newly diagnosed multiple myeloma was active with manageable toxicity and excellent stem cell yields. The incorporation of bortezomib as a consolidation therapy improved the clinical outcome with the expense of rather frequent development of peripheral neuropathy.