Rapid Remission Induction by VTD (Velcade, Thalidomide, Dexamethason) in Patients with Multiple Myeloma and High Tumor Burden at Diagnosis.

Background: VTD was reported to be an active salvage regimen in patients with relapsed/refractory multiple myeloma (MM). Since initial results with VTD as frontline therapy were also promising, we used VTD as induction treatment prior to autologous transplantation in MM patients with particularly high tumor burden.

Methods: Velcade was administered at 1.3 mg/m² on days 1, 4, 8, and 11; thalidomide was given as a daily dose of 100 mg; dexamethasone (20 mg per os) was given on days 1, 2, 4, 5, 8, 9, 11, and 12. Four cycles were scheduled every 3 weeks.

Results: We here report on three patients (age 36, 38, and 50 years) with newly diagnosed MM and high tumor mass at presentation (patient 1: Bence-Jones kappa MM with 95% plasma cell infiltration, serum free-kappa light-chains 4000 mg/l; patient 2: IgG-kappa MM with serum IgG > 9000 mg/dl, bulky plasmacytomas in the iliac bones; patient 3: IgA-lambda MM with 70% plasma cells in the bone marrow, IgA 4500 mg/dl, plasmacytoma in the os sacrum > 10 cm in diameter). Genetically, all 3 patients corresponded to the hyperdiploid variant (multiple trisomies, absence of del(13q14) and del(17p13)); patient 1 also had a t(11;14) and gain of chromosome 1q21. VTD resulted in a paraprotein reduction of at least 75% already after cycle 1. Rapid tumor mass reduction was not associated with signs of tumor lysis, and patient 1 had a significant improvement in renal function (serum creatinine from 2.4 to 1.3 mg/dl). After 4 cycles of VTD, patients 1 and 2 achieved a CR including a normal kappa/lambda ratio in the free-light-chain assay (patient 3 still ongoing). Patients have already completed G-CSF primed peripheral stem cell collection and autologous transplantation. Toxicity of VTD was mild (transient nausea and diarrhea in patient 2), in particular no peripheral neuropathy (grade 2 or higher). 7 additional pts are still at an early phase of VTD treatment, and data will be available at the meeting.

Conclusion: Induction treatment with VTD results in an effective tumor mass reduction already within one cycle and should be further evaluated in MM patients in need of rapid disease control.