CHICAGO—The combination of cyclophosphamide(Drug information on cyclophosphamide), bortezomib(Drug information on bortezomib), and dexamethasone(Drug information on dexamethasone) is associated with high rates of response and manageable toxicity among patients with newly diagnosed multiple myeloma, according to results from a single-arm phase II trial.
Patients with newly diagnosed multiple myeloma were treated with four 28-day cycles of cyclophosphamide, bortezomib (Velcade), and dexamethasone. The regimen, also known as CyBorD, was associated with a 90% drop in M protein levels aft er cycle four.
“Most of the reduction in monoclonal protein occurred within the first two cycles of therapy,” pointed out lead investigator Craig B. Reeder, MD, a hematologist at the Mayo Clinic in Scottsdale, Ariz.
“Growth factors were allowed after cycle 1, bisphosphonates were felt to be a standard part of care, and it was strongly recommended that patients receive prophylaxis with acyclovir, a quinolone antibiotic, and a proton pump inhibitor,” he noted (ASCO 2008 abstract 8517).
Analyses were based on 33 patients with a mean age of 60 years. In terms of cytogenetics, 48% of the patients had del(13) and 21% had t(4;14).
In an intent-to-treat analysis, the proportion of patients with at least a very good partial response after cycle four (the trial’s primary endpoint) was 61%, with 39% having a complete or near-complete response. In an analysis restricted to the 28 patients completing all four cycles, the proportion of patients with at least a very good partial response was 71%, with 46% having a complete or near-complete response.
Stem cell mobilization was performed in 21 patients. In all cases, the number of stem cells collected was adequate for transplantation, at more than two million, and in 81% of cases, more than five million cells were collected. “This confirms our suspicion that this regimen is not toxic to stem cells,” Dr. Reeder commented.
Some 23 patients underwent transplantation, 18 of whom were evaluable. In this subset, the post-transplantation rate of complete or near-complete response was 72%. Among the 10 patients who did not undergo transplantation, the leading reasons were high-risk genetics (three patients) and study discontinuation due to toxicity (three patients).
Some 48% of patients had grade 3 adverse events, and 13% had grade 4 adverse events. The most common of these were thrombocytopenia, neutropenia, hyperglycemia, and anemia. However, 84% of patients developed thrombocytopenia of any grade, and 66% developed neuropathy of any grade.
“This was enough in our minds to warrant changing the regimen in a follow-up study,”
Dr. Reeder said. There were nine dose reductions for bortezomib, seven for cyclophosphamide, and 11 for dexamethasone. “Most of the dose reductions for bortezomib and dexamethasone occurred late, in cycle three and cycle four,” he pointed out. Dr. Reeder concluded that the CyBorD regimen is highly active in this setting, has manageable toxicity, and allows successful stem cell collection. “The future involves reopening this trial for an additional 30 patients,” he said, noting that bortezomib will be given less frequently and the dexamethasone dose will be reduced after the first two cycles.
“This regimen is going to be studied as part of a three-arm randomized trial for upfront therapy in multiple myeloma,” he added.
The Vantage Point on this article can be found here:
Rate of response to CyBorD is ‘truly remarkable’