HOVON 50/GMMG-HD3-Trial: Phase III Study on the Effect of Thalidomide Combined with High Dose Melphalan in Myeloma Patients up to 65 Years.

The joint phase-III HOVON50/GMMG-HD3 trial was designed to assess the effect of thalidomide in induction treatment and as maintenance after high-dose therapy (HDT) and autologous stem cell transplantation (SCT) for multiple myeloma (MM). The standard treatment arm comprised 3 cycles of VAD, mobilisation with CAD+G-CSF (cyclophosphamide 1000 mg/m², day 1; adriamycin 15 mg/m², days 1–4; dexamethasone 40 mg, days 1–4; G-CSF until end of harvest), HDT with 1 or 2 cycles of melphalan 200 mg/m², followed by autologous peripheral blood SCT (PBSCT), and maintenance with interferon-alpha (9 mio. U per week). In the experimental arm, TAD (thalidomide, 200 mg for HOVON / 400 mg for GMMG; adriamycin 9 mg/m², days 1–4; dexamethasone 40 mg, days 1–4, 9–12, 17–21) was used for induction treatment. Mobilisation and HDT were identical to the standard arm. Experimental maintenance was thalidomide (50 mg per day). A first group of 406 patients (of 1050 included) are evaluable for the comparison of VAD vs. TAD and response after 1st HDT. A trend for a higher toxicity was observed in the TAD- compared with the VAD-arm (drop out: 15% vs. 8%, p= 0.10). Low molecular weight heparin was effective in the prevention of deep venous thrombosis during TAD-treatment (DVT-incidence 8% vs. 4% p= 0.15). The median number of stem cell collections to harvest at least one autograft was 1 in both arms (p= n.s.). Treatment-results are presented in table 1. In a subgroup of 90 GMMG-patients, 78% and 74% compared with 62% and 54% still received thalidomide compared with interferon-alpha at 12 and 24 months after start of maintenance. In summary, thalidomide+AD induce a significantly higher response rate, but this effect is completely offset by HDM. Therefore, results on EFS/PFS are necessary before thalidomide containing regimens can be defined as a standard for induction treatment before HDT. The maintenance treatment with thalidomide is better tolerated compared with interferon-alpha.