The researchers, led by Andrzej J. Jakubowiak, MD, PhD, professor of medicine and director of the multiple myeloma program at the University of Chicago Medical Center, found that combining carfilzomib, a next generation proteasome inhibitor, with two standard drugs — lenalidomide and low-dose dexamethasone compared favorably to other frontline regimens.
The longer patients stayed on the therapy, the better their response. After at least eight 28-day cycles of treatment, 61 percent of the 36 patients who remained on the therapy had a stringent complete response, defined as no detectable tumor cells or myeloma protein in the blood or bone marrow; 78 percent had at least a near complete response. More than 90 percent of patients had no progression of their disease at two years.
“These rapid and durable response rates are higher than those achieved by the best established regimens for newly diagnosed multiple myeloma,” said Jakubowiak. “We have observed excellent efficacy, the best reported to date, and very good tolerability, including limited peripheral neuropathy that has been problematic with other drug combinations.”
The research team enrolled 53 patients in the trial at four centers. Patients, aged 35 to 81, all had newly diagnosed multiple myeloma. Every patient received all three drugs and the carfilzomib dose levels were increased twice for new patients as the study progressed. Most patients responded rapidly to the combination and continued to improve.
“Newly diagnosed patients with myeloma are most sensitive to treatment,” Jakubowiak said. “A rapid and sustained response to the initial phase of treatment, as in the case of this study, can typically project longer remission, and, possibly, longer overall survival.”
Multiple myeloma is a cancer that arises in plasma cells, the bone marrow component that produces antibodies. The American Cancer Society estimates that about 21,700 Americans will be diagnosed with multiple myeloma in 2012 and 10,710 will die from the disease.
The Multiple Myeloma Research Consortium, Onyx Pharmaceuticals Inc., Celgene Corp. and the University of Michigan funded the study.
Additional authors include Kent Griffith, Tara Anderson, Brian Nordgren, Kristen Detweiler-Short, Daniel Lebovic, Ammar Al-Zoubi, Asra Ahmed, Melissa Mietzel, Daniel Couriel, Terri Jobkar, and Mark Kaminski from the University of Michigan; Dominik Dytfeld from Poznan University of Medical Sciences, Poznan, Poland; David Vesole from Hackensack University Medical Center, Hackensack, NJ; Sundar Jagannath from Mount Sinai Medical Center, New York, NY; Keith Stockerl-Goldstein and Ravi Vij from Washington University, St. Louis, MO; Sandra Wear from the Multiple Myeloma Research Consortium, Norwalk, CT; Mohamad Hussein from Celgene Corporation, Summit, NJ; and Homa Yeganegi from Onyx Pharmaceuticals, South San Francisco, CA.
ASCO Presentation: Session: Myeloma, Abstract #8011; Sunday June 3, 8:00 AM to 11:00 AM, Room E354a: “Stringent complete response in patients with newly diagnosed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone.”
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