Stem Cell Transplant Continues to Be the Best Option in Multiple Myeloma

Findings from a phase 3 clinical trial note that patients with multiple myeloma who receive upfront autologous stem cell transplant (ASCT) typically live longer without disease progression those those who only receive chemotherapy. The results of the study were presented before the 2015 American Society of Clinical Oncologists (ASCO) Annual Meeting.

“For the past 10 to 15 years, therapies with novel non-cytotoxic drugs have increased the response rate and significantly improved survival in previously untreated patients. The remarkable activity of novel therapies has recently questioned the role of upfront ASCT for patients with multiple myeloma,” said lead study author Michele Cavo, head of the Seràgnoli Institute of Hematology at the University of Bologna School of Medicine. “However, our findings show that 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.”

The large prospective, multicenter, intergroup, randomized phase 3 study, which was conducted by the European Myeloma Network (EMN), included 1,266 patients who were newly diagnosed with multiple myeloma. Following induction therapy with Velcade (bortezomib)-cyclophosphamide-dexamethasone (VCD) patients were randomly assigned to receive either Velcade -melphalan-prednisone (Deltasone) (VMP) or high dose Alkeran (melphalan) followed by single ASCT. In treatment centers with a standard policy of performing two ASCTs, patients were randomly assigned to either VMP with single or double ASCT.

In the second stage of the study, patients in both groups were randomized to receive a Velcade -based consolidation therapy or no consolidation therapy. Finally, all patients received Revlimid (lenalidomide) maintenance until progression or intolerable toxicity.

The primary endpoint of the study was the probability of surviving without progression of the disease starting from the first randomization. The first pre-specified interim analysis was performed in January 2016.

After a median follow-up of 23.9 months, median progression-free survival (PFS) was not yet reached, but data showed that patients who received ASCT progressed more slowly than those who received VMP therapy without transplant, said Cavo.

Among patients that had not yet experienced disease progression, those randomized to upfront ASCT had a 24 percent reduction in the risk of progressing at any future time point compared with those randomized to chemotherapy alone including Velcade. The difference between the two groups was statistically significant, said Cavo.

Certain subgroups of patients experienced an additional benefit with ASCT. Patients with advanced disease according to International Staging System that were randomized to the ASCT arm, had a 48 percent lower chance of progressing at the next analysis compared to those not receiving transplant.

Among patients with high-risk cytogenetics including 17p deletion, ASCT was associated with a 28 percent lower chance of future progression compared to VMP therapy without transplant.

Those receiving ASCT were also more likely to achieve a high quality response with at least 90 percent tumor cell mass reduction to treatment compared with patients who did not have a transplant (84 percent and 74 percent, respectively). This is an important indicator of longer survival, said Cavo.

“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, including the novel agent Velcade,” said Cavo. “The superior efficacy of high dose chemotherapy and ASCT over chemotherapy including Velcade is further supported by the significant enhanced probability of achieving a high quality response.”

For patients at a low risk of relapse, a longer follow-up is required to carefully compare the different arms of the study. Interim analysis of data related to the second randomization to consolidation therapy or no consolidation therapy is not yet complete. The study is ongoing, and future analyses will assess overall survival, toxicity and quality of life as well as other measures.

The FDA approved Velcade for the treatment of patients with multiple myeloma in 2008 based on an international, multicenter, open label, active-control trial in previously untreated patients with symptomatic multiple myeloma. HDM with ASCT has been traditionally considered the standard of care for younger and fit patients with newly diagnosed multiple myeloma.