ISY3-1 - Treatment of transplant-eligible patients with newly diagnosed multiple myeloma

Abstract

For the past 20 years, high-dose chemotherapy plus autologous stem cell transplantation (ASCT) has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. After the introduction of new agents of proteasome inhibitors and immunomodulatory drugs such as bortezomib, thalidomide and lenalidomide, effective induction therapy for transplant-eligible patients has been developed and now two or three drug combinations with a backbone of bortezomib has been widely used. After 3 or 4 courses of induction therapy, peripheral blood stem cells are collected with high-dose cyclophosphamide plus G-CSF or G-CSF alone and ASCT is performed after high-dose melphalan conditioning. In addition, post-transplant consolidation and maintenance could lead increased rates of minimal residual disease (MRD) negativity. However, this treatment requires hospitalization and can be associated with substantial toxic effects. The improved efficacy of novel agents has raised questions about the role and timing of transplantation in the era of novel agents. To address these issues, Intergroupe Francophone du Myelome conducted a phase 3 trial to compare the efficacy and safety of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) alone with the efficacy and safety of RVD plus ASCT for the treatment of newly diagnosed multiple myeloma in adults up to 65 years of age. RVD therapy plus ASCT was associated with significantly longer progression-free survival than RVD therapy alone. Although overall survival did not differ significantly between the two approaches, ASCT remains as a standard of care even VRD induction regimen is used. The use of a combination therapy that incorporates newer proteasome inhibitors, next-generation immunomodulatory drugs, and potent monoclonal antibodies along with transplantation tailored according to MRD detection could further improve outcomes among adults up to 65 years of age with multiple myeloma.