Mieloma multiplo: identificazione di fattori prognostici, biomarcatori di risposta alla terapia, evoluzione clonale e di terapie innovative e personalizzate.

In the era of new drugs, the role of high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation (ASCT) in newly diagnosed multiple myeloma patients (NDMM) has been questioned. The European Myeloma Network proposed the multi-centric clinical trial, prospective, phase III EMN02/HO95 MM which compared, in over 1500 patients, the efficacy of intensification therapy with Bortezomib, Melphalan and Prednisone (VMP) to high-dose Melphalan (HDM) and subsequent ASCT in NDMM patients aged 65 years. In addition, this trial compared the role of consolidation with Bortezomib, Lenalidomide and Desametasone versus no consolidation and the efficacy of single (ASCT-1) versus double ASCT (ASCT-2). The final analysis of the study confirmed ASCT as the standard of care for NDMM young patients. It is able to guarantee a better quality of response (≥VGPR response, 84 % vs 77%; p=0.0020) and a prolonged PFS (median of 56.7 months vs 41.9 months), also in the subgroups of patients with high risk cytogenetic features for del(17p) ± t(4;14) ± t(14;16). In a follow-up of over 6 years, ASCT was associated with a significant extension of OS (OS estimated at 75 months 69% for ASCT arm compared to 63% for VMP arm, p=0.034) and a longer-lasting control of the disease compared to intensification therapy with new drugs (PFS2 estimated at 75 months 57% versus 49% and median TTnT of 66 months versus 47 months, respectively). The comparison between ASCT-1 and ASCT-2 showed that ASCT-2 ensures prognostic improvement of both PFS (HR 0.74) and OS (HR 0.62), with particularly benefit in patients with del(17p) (HR for progression 0.24 or death 0.30).