RVD Plus Transplantation Delayed Progression in Myeloma

Combined treatment with lenalidomide, bortezomib, and dexamethasone plus transplantation significantly delayed progression in patients with multiple myeloma.

Combined treatment with lenalidomide, bortezomib, and dexamethasone (RVD) plus transplantation significantly delayed progression in patients with multiple myeloma compared with RVD alone; however, results from the Intergroupe Francophone du Myélome 2009 study showed no difference in overall survival between the two approaches. The results of the study were published in the New England Journal of Medicine.

“This benefit must be weighed against the increased risk of toxic effects associated with high-dose chemotherapy plus transplantation, especially since we found that later transplantation might be as effective as early transplantation in securing long-term survival,” wrote Michel Attal, MD, of the Institut Universitaire du Cancer de Toulouse-Oncopole in Toulouse, France, and colleagues. “Our results suggest that 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 minimal residual disease detection could further improve outcomes among adults up to 65 years of age who have multiple myeloma.”

High-dose chemotherapy plus transplantation has been the standard of care for patients with myeloma for many years. However, recent studies of immunomodulatory drugs and proteasome inhibitors have shown activity in patients with this disease. Studies showing the benefits of these drugs in combination with lenalidomide have led researchers to question the role and timing of transplantation in initial treatment of these patients.

In this phase III trial, 700 patients with multiple myeloma were randomly assigned to induction therapy with 3 cycles of RVD and consolidation therapy with either 5 additional cycles of RVD (n = 350) or high-dose melphalan plus stem cell transplantation followed by 2 additional cycles of RVD (n = 350). All patients received lenalidomide maintenance therapy for 1 year.

Patients assigned to RVD plus transplantation had a median progression-free survival of 50 months compared with 36 months in patients assigned RVD alone (adjusted hazard ratio, 0.65; P < .001). Improved progression-free survival was seen in all patient subgroups, including those stratified by International Staging System stage and cytogenetic risk.

Patients assigned to transplantation also had a higher rate of complete response compared with RVD alone (59% vs 48%; P = .03). Additionally, more patients in the combination group had no minimal residual disease detected (79% vs 65%; P < .001).

Despite the improvement in progression-free survival, overall survival at 4 years was not significantly different between the transplantation group and the RVD-alone group. Overall survival was longer in patients in whom minimal residual disease was not detected (P < .001).

“These results might be related to the use of RVD therapy in both treatment groups and to the high level of activity of the new agents that were used to treat relapses,” the researchers noted. “The similarity in overall survival in the two groups may also be related to the successful use of salvage transplantation.”

Patients assigned to transplantation had significantly higher rates of grade 3 or 4 neutropenia (92% vs 47%), gastrointestinal disorders (28% vs 7%), and infections (20% vs 9%).