Multicenter phase 2 trial of a curative strategy for high-risk smoldering myeloma

Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). A multicenter phase 2 trial in Spain evaluated a treatment approach employed for patients with newly diagnosed MM as curative strategy for high-risk smoldering myeloma. Patients received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd) followed by high-dose melphalan autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, an Rd maintenance for 2 years. Three months after HDM-ASCT, undetectable measurable residual disease (uMRD) was seen in 62%, and 4 years after HDM-ASCT this was sustained in 31%. Five of 90 patients progressed to MM, and biochemical progression was seen in 36 patients; failure to achieve uMRD at the end of treatment predicted biochemical progression. The 70-month overall survival rate was 92%. Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment-related death. Three second primairy malignancies have been reported. The authors conclude that this curative approach resulted in 31% of patients maintaining uMRD 4 years after HDM-ASCT.