Less intensive treatment with bortezomib—giving the drug weekly rather than twice weekly —appears to have comparable efficacy but less toxicity, according to a study by Spanish researchers. Good results were reported with the less-intensive regimen in newly diagnosed older patients.
"We were trying to optimize the treatment of elderly patients, so we tried a less intensive weekly administration for induction, followed by maintenance doses given every 3 months," said lead researcher Maria-Victoria Mateos, MD, PhD, from University Hospital in Salamanca, Spain.
The study included 260 elderly patients, who were treated with either bortezomib with melphalan and prednisone (VMP) or bortezomib with thalidomide and prednisone (VTP), both given for six cycles. In the first cycle patients received bortezomib twice weekly, but in subsequent cycles just once weekly. For maintenance, patients received bortezomib plus either thalidomide or prednisone for up to 3 years.
Both induction approaches were highly effective, producing response rates of about 80%; both approaches were also effective in the maintenance setting, increasing the rate of complete response from 23% to 42% during maintenance.
There was a clear difference, however, in the toxicity profiles of the induction regimens, Mateos reported. The VMP regimen was associated with more grade 3 neutropenia and more grade 3 infections, which can be managed with growth factor support, she noted. The VTP regimen was associated with more serious cardiovascular events and more severe peripheral neuropathy, which she considered more important.
"We found that melphalan is probably the best partner for bortezomib in elderly untreated myeloma patients because the efficacy is similar to VTP, but the toxicity profile is different. There are more neutropenias but less cardiotoxicity and peripheral neuropathies with VMP," she said.
"We asked whether we could achieve similar efficacy with a less intensive bortezomib regimen, and the answer is that clearly we can," she concluded. She added that perhaps the most important finding was that the poor prognosis of high-risk elderly patients could be overcome with either regimen.
The investigators are now evaluating whether thalidomide can be replaced with lenalidomide for both induction and maintenance therapy, with the hope of further reducing toxicity.