The use of novel agents in multiple myeloma has led experts to question whether autologous stem-cell transplant (ASCT) is warranted upfront, or whether it can be used as effectively after patients relapse.
The results of the IFM/DFCI-2009 trial, which were presented at ASH 2015 by Michel Attal, MD, Institut Universitaire du Cancer de Toulouse-Oncopole, France, suggest that transplant is still preferred.
“In the era of new drugs, transplantation should remain a standard of care for young patients with de novo myeloma,” said Dr Attal.
In the second interim analysis of IFM/DFCI-2009, the patients who received a triplet therapy on diagnosis followed by ASCT achieved a significantly longer progression-free survival (PFS) than those who received a triplet therapy and underwent transplant if they relapsed.
IFM/DFCI-2009 was a prospective, randomized trial comparing ASCT to nontransplant in 700 previously untreated patients who were candidates for ASCT. The patients were randomly assigned to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD) for 8 cycles with stem-cell mobilization but no immediate transplant, or to RVD plus ASCT. Patients in both arms received 1 year of maintenance therapy with lenalidomide.
At the time of the second interim analysis, the independent Data Safety and Monitoring Committee recommended stopping the trial based on the superiority of the transplant arm in multiple outcomes.
At most time points, more patients in the transplant arm achieved higher response rates and higher rates of very good partial response or better, which was true for all of the subgroups. Most important, at a median follow-up of 41 months, the PFS was significantly improved in the transplant arm (43 months) versus in the nontransplant arm (34 months), and the 4-year PFS rates were 47% and 35%, respectively (hazard ratio, 0.69; P <.001). All subgroups of interest had better outcomes after having ASCT.
The overall survival data were immature, and there are currently no differences between the arms; more than 80% of patients in each arm are alive at 4 years.
There is an ongoing US trial that has a similar design, but the patients in the trial are administered maintenance lenalidomide continuously until progression in both arms. The results of this trial remain crucial for determining whether the PFS benefit of transplant is maintained in a setting where maintenance treatment is continued, Dr Attal said.
The best news from this study is that “the shape of the survival curve is spectacular—83% at 4 years,” said S. Vincent Rajkumar, MD, Professor of Medicine, Mayo Clinic, Rochester, MN, who commented on the study. “That means we can continue to randomize patients to early versus late transplant, and we can continue to offer delayed transplant to standard-risk patients who prefer to delay it.”