Abstract

Background: Incorporation of novel agents has resulted in improved response rate and reduced side effects in multiple myeloma. Especially in newly diagnosed multiple myeloma, novel agents are very promising as induction chemotherapy.

Methods: Patients are planned to receive 2 cycles of VAD (vincristine 0.4mg D1–4, adriamycin 9mg/m2 D1– 4, dexamethasone 40mg D1–4, 9–12 every 3 weeks), and VTD (bortezomib 1.3mg/m2 D1, 4, 8, 11, thalidomide 100mg daily, dexamethasone 40mg D1–4, 9–12 every 3 weeks). High dose melphalan (200mg/m2) is used as a conditioning regimen for ASCT. Bortezomib (1.3mg/m2) as a maintenance treatment is administered weekly x 4 times every 6 weeks for 4 cycles after ASCT. Response was assessed by EBMT criteria, with additional category of nCR. Adverse events were graded by the NCI-CTCAE, Version 3.0.

Results: Total 71 patients were enrolled, and efficacy could be assessed in 62 patients. After 2 cycles of VAD, response rate was 71% (95% CI, 59.7–82.3). After VTD, overall response rate was more increased to 96% (95% CI, 90.8–100, rate of CR and nCR 27%). Especially, nine patients with poor prognostic cytogenetics all showed response after VTD. So far, autologous stem cells were successfully collected in 42 patients with a median CD34+ count of 6.49 x 106/kg (range, 0.6–44.7 x 106/kg) except one patient. After autologous stem cell transplantation, twenty five patients completed bortezomib maintenance, and the rate of CR + nCR was 68%. The median follow-up duration was 16.4 months, and median time to response was 1.6 months. Median time to progression was not reached, and 1 year survival rate was 98%. In total, 127 cycles of VAD and 115 cycles of VTD were given and grade 3,4 hematologic toxicity was more frequently observed after VAD than VTD (anemia 18.1% vs 8.7%, neutropenia 12.6% vs 4.3%), and incidence of grade 3 peripheral neuropathy after VAD was lower (1.5%) than VTD (7%). All patients received low-dose aspirin prophylaxis. Deep vein thrombosis was observed in two patients, but this was not related with thalidomide.

Conclusions: Sequential VAD and VTD induction therapy in newly diagnosed multiple myeloma was very effective, even in patients with poor prognostic cytogenetics, and did not prejudice stem cell collection. VTD as induction therapy has contributed to increased response rate and decreased side effects. *Protocol Number : KMM51-NCT00378755

Disclosures: No relevant conflicts of interest to declare.

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