Minimal residual disease and log-reduction of plasma cells are associated with superior response after double autologous stem cell transplant in younger patients with multiple myeloma

Background: Optimization of chemotherapy regimens in the treatment of multiple myeloma (MM) has led to increase the frequency of cases with complete response (CR). Nonetheless, many MM patients still experience relapse, suggesting that CR represents a suboptimal response criteria, and that new therapeutic strategies are needed after single transplant. However, the role of double autologous stem cell transplant (ASCT) as new adjunctive strategy remains to be elucidated. Indeed, we investigated the role of minimal residual disease (MRD) and log-reduction of plasma cells (PCs) as predictors of outcome and in quantifying the degree of tumor reduction after any ASCT. Methods: MRD and log-reduction were assessed by a six-color flow cytometry (FC) at different time-points: post induction, post first-, and post-second ASCT. Results: A significant difference was evidenced among the three time points for both log-reduction (P < 0.001) and MRD (P = 0.005). MRD levels after double ASCT were lower than MRD levels achieved after single ASCT (P = 0.005) and after induction (P < 0.001). Frequency of MRD positive patients after double ASCT was significantly lower rather than after the first ASCT (P = 0.008) and after induction (P = 0.004). Interestingly, a significant reduction of PFS was observed in patients with an unfavorable-risk cytogenetic (P < 0.001) and patients with MRD over 0.01% (P = 0.001) as well as log-reduction lower than 2.57 (P = 0.018) after double ASCT. Conclusions: Our results show that a better clearance of myeloma cells is observed after the double ASCT, and a longer PFS is associated with a lower MRD.