CHICAGO — Upfront autologous stem cell transplantation (ASCT) remains the preferred treatment for patients age 65 years or younger with newly diagnosed multiple myeloma, according to phase 3 study results reported at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.1

These findings from the European Myeloma Network, “the largest conducted so far, was designed to primarily compare upfront ASCT vs chemotherapy alone, including bortezomib,” said Michele Cavo, of the Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy.

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The study compared 4 cycles of bortezomib-melphalan-prednisone (VMP) vs high-dose melphalan (HDM) and single or double ASCT (if centers applied a tandem ASCO policy) as intensification therapy after bortezomib-cyclophosphamide-dexamethasone induction and peripheral blood stem cell collection.

After VMP and HDM, consolidation therapy with bortezomib-lenalidomide-dexamethasone vs no consolidation was planned, followed by lenalidomide maintenance until disease progression or toxicity.

From February 2011 through April 2014, the study enrolled 1510 patients; of these, 1192 were included in the analysis, 497 in the VMP group, and 695 in the ASCT group.

At a median follow-up of 26 months, median progression-free survival from first randomization, the primary study end point, was found not reached in patients who received ASCT, compared with 44 months for the VMP arm (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.59-0.90; P = .003).

This benefit was retained across predefined patient subgroups, including those with revised ISS stage III (HR, 0.59; 95% CI, 0.56-0.97; P = .036) and high-risk cytogenetics [t(4;14) ± del(17p) ± del(1p) ± 1q gain] (HR, 0.69; 95% CI, 0.52-0.92; P = .010).

In addition, a “superior rate” of very good partial response or greater was observed among the patients who received ASCT (85.5%) compared with VMP (73.8%; P < .001).

When median progression-free survival was examined by single or double ASCT, it was not reached for either ASCT arm and was significantly longer at 3 years, 73.1% for double ASCT and 63.0% for single ASCT, compared with 57.5% for VMP. The HR for single ASCT was 0.81 (95% CI, 0.65-1.01; P = .06); double ASCT, 0.56 (95% CI, 0.41-0.77; P < .001); and, for double vs single ASCT, 0.69 (95% CI, 0.50-0.71; P = .03).

Grade 3/4 adverse events were higher in the ASCT arm; specifically, anemia was 15.8% compared with 0.6% in the VMP arm; neutropenia, 78.2% vs 79.4%; thrombocytopenia, 82.1% vs 15.3%, and febrile neutropenia, 17.5% vs 0.2%.

“Upfront HDM and ASCT continues to be the reference treatment choice for fit patients with newly diagnosed multiple myeloma, even in the novel agent era, and even in the prospective comparison with standard dose regimens, including bortezomib,” Dr. Cavo concluded.



1. Cavo M, Palumbo A, Zweegman S, et al. Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): A randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial). Oral presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.