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Millenium Pharmaceuticals
Results of a phase 3 trial suggest a 3-drug combination improves survival in newly diagnosed multiple myeloma (MM).
The trial showed that bortezomib, lenalidomide, and dexamethasone (VRd) could significantly
improve progression-free and overall survival when compared to lenalidomide and dexamethasone (Rd).
In addition, investigators said the risk-benefit profile of VRd was acceptable.
The team noted, however, that grade 3 or higher neurologic adverse events (AEs) were more common with VRd than with Rd.
“Our results are clear,” said principal investigator Brian G.M. Durie, MD, of Cedars-Sinai Outpatient Cancer Center in Los Angeles, California.
“Using bortezomib in combination with lenalidomide and dexamethasone in frontline treatment—hitting the disease early and hard—makes a meaningful difference for myeloma patients. Our results represent a potential new standard of care.”
Dr Durie and his colleagues reported the results of this trial in The Lancet.
The research was funded by Millennium Pharmaceuticals, Takeda Oncology Company, Celgene Corporation, the National Institutes of Health, the National Cancer Institute, and the National Clinical Trial Network.
The trial enrolled 525 adults with MM. The patients ranged in age from 28 to 87, had active MM, and had not had any prior treatment for their disease.
The patients were randomized to 2 treatment groups. One group received Rd for 6 cycles over 6 months. The other group received VRd for 8 cycles over 6 months.
Results
The median follow-up was 55 months. In the VRd group, 241 patients were evaluable for safety and 216 for response. In the Rd group, 226 patients were evaluable for safety and 214 for response.
The overall response rate was 82% (176/216) in the VRd group and 72% (153/214) in the Rd group. The complete response rates were 16% (34/216) and 8% (18/214), respectively.
The median progression-free survival was 43 months in the VRd group and 30 months in the Rd group. The hazard ratio was 0.712 (P=0.0018).
The median overall survival was 75 months in the VRd group and 64 months in the Rd group. The hazard ratio was 0.709 (P=0.025).
The rate of grade 3 or higher AEs was 82% in the VRd group and 75% in the Rd group. The rate of discontinuation due to AEs was 23% and 10%, respectively.
Grade 3 or higher neurologic AEs were more frequent in the VRd group than in the Rd group—33% and 11%, respectively (P<0.0001).
There were 2 treatment-related deaths in the VRd group but none in the Rd group. And 10 patients in each group had a second primary malignancy.
“This is a landmark study that lends clarity to frontline therapy of myeloma,” said study author S. Vincent Rajkumar, MD, of Mayo Clinic in Rochester, Minnesota.
“Newer alternatives to VRd may be more expensive, cumbersome, or toxic. These regimens will therefore need to show superiority over VRd in randomized trials.”
Also worth noting, Dr Rajkumar said, is that the VRd regimen will become even more cost-effective as the drugs in this combination become generic over time.
