Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).

BACKGROUND High-dose chemotherapy with autologous stem cell transplantation has been the standard treatment for young patients with newly diagnosed myeloma. However, promising emerging data with the combination of lenalidomide, bortezomib and dexamethasone (RVD) have raised questions about the role of transplantation. METHODS We randomly assigned 700 patients to the RVD group (eight cycles; 350 patients) or to the transplant group (three cycles of RVD, followed by high-dose melphalan plus stem cell transplantation, followed by two additional cycles of RVD; 350 patients). Patients in both arms received maintenance lenalidomide for 1 year. The primary end point was progression-free survival. RESULTS Progression-free survival was significantly longer in the transplant versus the RVD group (median, 50 months vs. 36 months; hazard ratio, 0.65; P<0.001). This benefit was observed across all patient subgroups, including those stratified by International Staging System stage and cytogenetic risk profile. Transplantation versus RVD alone was associated with increased complete response (59% vs. 48%; P=0.006), and minimal residual disease negativity (79% vs. 65%; P<0.001). Overall survival was similar in both arms (4-year survival, 81% in the transplant group vs. 82% in the RVD group). Grade 3 or 4 neutropenia was significantly more common with transplantation than with RVD (92% vs. 47%), as were gastrointestinal adverse events (28% vs. 7%) and infections (20% vs. 9%). Rates of treatment-related deaths, second primary malignancies, thromboembolic events, and peripheral neuropathy were similar in the two treatment groups. CONCLUSIONS RVD plus transplant significantly prolonged progression-free survival as compared with RVD alone without overall survival difference.

Among the many parameters that can be analyzed by this method, the capillary size, the frequency distributions of diameters and lengths, the fractal nature of these networks, and the depth-related density of vessels are all vital features for an adequate model of cerebral microcirculation.

Key Points MRD using NGS-identified patients with an excellent outcome in multiple myeloma. MRD should be assessed in every prospective trial, and is a candidate to become a primary end point.

CC cannot be used to predict sarcopenia defined using DEXA but provides valuable information on muscle-related disability and physical function.

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Sarcopenia is not associated with physical difficulties in the absence of obesity. However, in the presence of obesity, sarcopenia tends to add difficulty for some physical functions.

The transplantation program with RVD induction and consolidation followed by lenalidomide maintenance produced high-quality responses and showed favorable tolerability in patients with newly diagnosed MM. Overall, 68% of patients achieved MRD negativity; none of these patients relapsed. This program is being evaluated in the ongoing IFM/Dana-Farber Cancer Institute 2009 phase III study.