Induction therapy and the role of stem cell transplantation in the treatment of myeloma multiplex in patients aged below 65 years

Therapeutical concept for myeloma mulitplex (MM) patients has been significantly improved over the previous years. As in other haematological malignancies, in MM also, induction treatment goal is to achieve complete remission (CR) of the disease. The importance of CR on overall survival (OS) in MM was first estimated in the high dose chemotherapy (CT) with autologous stem cell transplantation (ASCT). Induction treatment with 3-6 cycles of combined CT based on Dexamethason (VAD) following with one or two courses of high doses of Melphalan with ASCT leads to 20-40% CR and 40-55% CR/VGPR with median survival of 4-5 years. These are significantly better results compared to previous conventional therapy, and considering such findings, ASCT became the treatment of choice for MM patients aged below 65 years. The introduction of novel agents, such as immunomodulatory drugs (Thalidomid, Lenalidomid) and proteasome inhibitors (Bortezomib) into induction therapy have improved treatment of MM patients even more. The combination of Dexamethason with Thalidomid, Bortezomib or Lenalidomid, on the average in 3-4 cycles, arises the level of CR/VGPR (very good partial response) even to 60-75%. Bortezomib based regimens are recommended in the treatment of "high risk" group of patients with MM. Recommended conditioning regimen is 200 mg/m2 of Melphalan. If either CR or VGPR is not achieved, recommendation is to perform the second ASCT as a part of tandem"concept. Thalidomid applied as a "maintenance therapy" after ASCT may prolong OS. Until now, allogeneic ASCT, as the first line treatment for MM patients aged below 65 years, has been applied only in clinical trials.