Persistent Survival Benefit in Patients with Untreated Disease Treated with Bortezomib Added to Melphalan and Prednisone

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A final analysis of the phase III VISTA trial (Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone) found a persistent significant benefit in overall survival with VMP (bortezomib, melphalan, prednisone) vs MP (melphalan, prednisone) in patients with multiple myeloma who were ineligible for transplantation. At a median follow-up of 60.1 months (range, 0–74 months), median overall survival was 56.4 months for patients receiving VMP vs 43.1 months for patients receiving MP, a 31% reduced risk of death (HR = 0.695; P < .001). In addition, there is “no emerging safety signal for second primary malignancies following VMP,” investigators reported in the Journal of Clinical Oncology.

A total of 682 patients at 151 sites in 22 countries were randomly assigned to receive up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. The overall median age was 71 years.

“[Overall survival] benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min),” the researchers reported. “However, no significant difference was observed in the small subgroup with documented high-risk cytogenetics (n = 46).”

Most patients (63% of the VMP group and 73% of the MP group) received subsequent therapy. The median time to next therapy was longer in the VMP group, 30.7 months vs 20.5 months in the MP group (HR = 0.557, P < .001). “Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR = 0.914),” the authors wrote.

“Incidence proportions of all malignancies and of fatal hematologic malignancies and solid tumors were similar between arms,” the researchers reported. “Nineteen (6%) of 327 patients in the VMP arm and 13 (4%) of 328 patients in the MP arm reported second primary malignancies. Three patients (1%) in each arm had hematologic malignancies: Two patients in each arm had acute myeloid leukemia (fatal in all four patients), one patient in the MP arm had B-cell non-Hodgkin lymphoma that was fatal, and one patient in the VMP arm had myelodysplastic syndrome.”

The authors concluded that the final findings of the VISTA phase III trial “demonstrate a persistent significant [overall survival] benefit with VMP vs MP. These data are highly robust because of the large patient population and lengthy follow-up and show that VMP resulted in a substantial long-term [overall survival] benefit, with a 13.3-month increase in the median.”

San Miguel JF, et al: J Clin Oncol, December 10, 2012 (early release online).