New Combination Therapy for Untreated Multiple Myeloma
Name of the Trial
Phase II Study of Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients (NCI-11-C-0221). See the protocol summary.
Dr. Ola Landgren, NCI Center for Cancer Research
Why This Trial Is Important
Multiple myeloma is a cancer of plasma cells, the white blood cells that normally produce antibodies. The proliferation of these abnormal plasma cells in the bone marrow interferes with the production of normal blood cells and can cause bone pain and bone fractures. Myeloma cell proliferation also leads to the overproduction of proteins known as “paraproteins” or M proteins, which are antibodies or parts of antibodies. These proteins build up in the blood, where they can cause kidney damage and other problems. Multiple myeloma cannot be cured with current therapies, and most patients die of their disease within 3 to 4 years.
Much research has been devoted to improving outcomes for people with multiple myeloma, and several new drugs have been developed in recent years that have helped prolong the lives of patients. New agents such as bortezomib (Velcade), a proteasome inhibitor, and lenalidomide (Revlimid), which stimulates the immune system and blocks the formation of tumor blood vessels, exploit the biological characteristics of multiple myeloma to delay disease progression. In spite of these advances, though, progression is almost inevitable. Therefore, doctors and patients are eager to identify new treatments that may further prolong the lives of those with multiple myeloma.
A new drug called carfilzomib (Kyprolis) may be a promising addition to the arsenal of available treatments. Similar to bortezomib, carfilzomib blocks the action of proteasomes, which are protein complexes inside cells that degrade, or breakdown, unneeded or damaged proteins, including those that regulate cell growth and a cell death mechanism called apoptosis. Proteasomes are also important in the differentiation of plasma cells, the blood cells involved in multiple myeloma. Doctors want to know if combining carfilzomib with other drugs used to treat multiple myeloma is safe and effective.
In this phase II trial, people with newly diagnosed multiple myeloma will be treated with carfilzomib, lenalidomide, and dexamethasone for eight 28-day treatment cycles. Doctors will evaluate the toxicity of the combination therapy, particularly the incidence of peripheral neuropathy, a common and often debilitating side effect of some drugs used to treat multiple myeloma. They will also assess patients’ responses to the treatment and conduct frequent blood tests, bone marrow biopsies, and molecular imaging tests throughout the study.
“We presented an interim analysis in December 2012 and showed that, in the first 20 patients enrolled in the study, 75 percent obtained complete remission, which is unprecedented in this disease,” Dr. Landgren said. “Of the patients who achieved complete remission, 10 were evaluated for minimal residual disease using very advanced flow cytometry of bone marrow cells, and all of those patients were found to have no minimal residual disease. There were also very few severe side effects, so this treatment looks very promising.”
Although blood stem cell transplantation is not part of this study, patients who are eligible for that procedure may have stem cells collected after four cycles of treatment in case stem cell transplantation is needed to address a future relapse.