Upfront Transplant Best for Younger Multiple Myeloma Patients

Undergoing upfront autologous stem cell transplantation (ASCT) is still the preferred treatment of choice for patients aged 65 or younger with newly diagnosed multiple myeloma, according to interim results of a phase III trial presented during a press briefing ahead of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in June (abstract 8000).

“Patients randomized to upfront high-dose chemotherapy and ASCT had a significant reduction in the risk of progression or death compared to those receiving only chemotherapy alone including the novel agent bortezomib,” said researcher Michele Cavo, MD, head of the Seràgnoli Institute of Hematology at the University of Bologna. “Upfront high-dose chemotherapy and ASCT continues to be the best treatment option for fit patients with newly diagnosed multiple myeloma, even in the novel agent era.”

According to Cavo, the use of upfront ASCT for multiple myeloma has been under some debate in the era of novel agents such as bortezomib, a proteasome inhibitor approved by the FDA in 2008 for upfront treatment of the disease.

In this study, the researchers enrolled 1,266 patients with newly diagnosed disease. After induction therapy with bortezomib/cyclophosphamide/dexamethasone, all patients were randomly assigned to either bortezomib/melphalan/prednisone (MVP) or high-dose melphalan followed by single ASCT.

A planned interim analysis was performed in January 2016. Median progression-free survival was not yet reached. With a median follow-up of 2 years, results showed a 24% improvement in progression-free survival among patients assigned to high-dose melphalan and ASCT (hazard ratio [HR], 0.76 [95% CI, 0.61–0.84]; P = .010).

According to Dr. Cavo, this improved progression-free survival was seen across multiple subgroups examined in the study. Specifically, patients with revised International Staging System stage III disease had a 48% improved progression-free survival with ASCT (HR, 0.52 [95% CI, 0.32–0.85]; P = .01) and those patients classified as having high-risk cytogenetics had a 28% improved risk (HR, 0.72 [95% CI, 0.54–0.97]; P = .03).

In addition to the improvements in progression-free survival, treatment with transplant was also associated with improved quality of response, with 84% of patients undergoing ASCT achieving a very good partial response compared with 74% of patients assigned to MVP (P < .0001).

Commenting on the study, ASCO President Julie M. Vose, MD, MBA, FASCO said: “I think this is a very important, very large study for those of us who take care of multiple myeloma patients, and we can now truly say that we have data to say that transplantation is still important even in the era of novel treatment.”

A second stage of the study had patients in both groups randomly assigned to consolidation therapy with bortezomib/lenalidomide/dexamethasone or no consolidation therapy with maintenance lenalidomide until progression. Interim analysis of data from this stage is not yet complete.