Clinical Pearls & Morning Reports
Published July 13, 2022
Richardson et al. conducted a phase 3 trial which compared autologous stem-cell transplantation (ASCT) to lenalidomide, bortezomib, and dexamethasone (RVD) in adults with newly diagnosed multiple myeloma. Read the NEJM Original Article here.
Q: Describe the Intergroupe Francophone du Myélome (IFM) 2009 trial.
A: The IFM 2009 trial, in which patients with myeloma received induction treatment with RVD alone or with high-dose melphalan plus ASCT, followed by lenalidomide maintenance therapy for 1 year, showed superior progression-free survival with the use of ASCT. These findings provided support for the benefit of ASCT in patients with newly diagnosed myeloma. In that trial, in which patients had multiple effective treatment options at relapse and in which many received ASCT after RVD alone, no overall survival benefit of RVD plus ASCT was evident after a median follow-up of more than 7 years.
Q: What was the specific treatment received in each of the two groups in the trial by Richardson et al.?
A: All the patients received one cycle of RVD. After this cycle, the patients were randomly assigned, in a 1:1 ratio, to the RVD-alone group or the transplantation group. Patients in both groups received two additional cycles of RVD, followed by stem-cell collection. Patients in the RVD-alone group then received five additional RVD cycles, whereas those in the transplantation group received high-dose melphalan plus ASCT and, on recovery (approximately day 60), two additional RVD cycles. Maintenance therapy in both groups consisted of daily lenalidomide.
A: The trial showed the superiority of ASCT-based first-line therapy with respect to progression-free survival among eligible patients with newly diagnosed myeloma, findings that confirm those of the IFM 2009 trial. At a median follow-up of 76.0 months, the risk of disease progression or death was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% CI, 1.23 to 1.91; P<0.001). The median duration of progression-free survival was 46.2 months (95% CI, 38.1 to 53.7) in the RVD-alone group and 67.5 months (95% CI, 58.6 to not reached) in the transplantation group. However, despite a median follow-up of more than 6 years in the trial, approximately one quarter of the patients had died, and given the lengthy median overall survival among patients in this population in general, the authors did not observe an overall survival advantage of RVD plus ASCT over RVD alone. The authors state that the lack of an overall survival benefit of RVD plus ASCT is probably associated with the multiple, highly efficacious options available after first-line therapy that have emerged over the past 10 years.
A: Treatment-related events of grade 3 or higher occurred in 279 patients (78.2%) in the RVD-alone group and 344 patients (94.2%) in the transplantation group; 60.5% and 89.9%, respectively, reported treatment-related hematologic adverse events of grade 3 or higher (P<0.001). Second primary cancers were reported in 37 patients (10.4%) in the RVD-alone group and 39 patients (10.7%) in the transplantation group (5-year cumulative incidence, 9.7% and 10.8%; P=0.90).