Upfront treatment with melphalan and autologous stem cell transplantation (ASCT) should be the standard treatment approach for younger patients with newly diagnosed multiple myeloma, according to the results of a pooled analysis published in Leukemia.
Patients who received treatment with upfront ASCT had a significant improvement in progression-free survival 1 (PFS1), PFS2, and overall survival compared with chemotherapy plus lenalidomide.
For this study, Francesca Gay, MD, of Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Italy, and colleagues pooled data from two phase III trials: RV-MM-209 and EMN-441. In these trials, patients with myeloma were randomly assigned to two courses of melphalan 200 mg/m2 (MEL200) and ASCT (n = 268) or chemotherapy plus lenalidomide (n = 261).
“The impressive survival improvement with novel agents (thalidomide, bortezomib, and lenalidomide) plus chemotherapy in the non-transplant setting has led clinicians to hypothesize that multiple myeloma could be managed without high-dose therapy or that high-dose therapy could be a valid salvage approach,” the researchers wrote. “This pooled analysis of the RV-MM-209 and EMN-441 trials showed that MEL200-ASCT significantly prolonged median PFS1 by 18 months in comparison with chemotherapy plus lenalidomide.”
Assignment to MEL200 and ASCT significantly improved PFS1 by about 1.5 years (median, 42 vs 24 months; hazard ratio [HR], 0.53; P < .001) and PFS2 by about 20% (4 years: 71% vs 54%; HR, 0.53; P < .001) compared with chemotherapy.
“The improvement in PFS2 suggests that most of the benefit observed during the first remission is maintained after relapse,” the researchers noted. “In some cases, ASCT may no longer be a feasible option at relapse, and even when administered at first relapse, may not induce a survival benefit comparable to upfront ASCT.”
Assignment to transplant also significantly prolonged overall survival at 4 years (84% vs 70%; HR, 0.51; P < .001) compared with chemotherapy. The researchers noted that these survival improvements were seen in patients with both good- and bad-prognosis disease.
A little more than half (53%) of patients who relapsed after assignment to chemotherapy plus lenalidomide received salvage ASCT at first relapse. Compared with salvage ASCT, upfront ASCT significantly reduced the risk for death (HR, 0.51; P = .007).
“Ongoing trials exploring the use of bortezomib plus lenalidomide or melphalan and future trials with monoclonal antibodies could help draw definitive conclusions on the role and timing of ASCT,” the researchers concluded.