ORLANDOIn heavily pretreated patients with relapsed or refractory multiple myeloma, the combination of lenalidomide (Revlimid) and bortezomib(Drug information on bortezomib) (Velcade), with or without dexamethasone(Drug information on dexamethasone), is active and well tolerated, according to results of an early phase trial. Paul G. Richardson, MD, Dana-Farber Cancer Institute, presented the results at the 48th Annual Meeting of the American Society of Hematology (abstract 405).
The objective of the study was to identify the maximum tolerated dose (MTD) and recommend a dose for phase II studies. Eight patient cohorts received combinations of two bortezomib doses (1.0 mg/m2 or 1.3 mg/m2 on days 1, 4, 8, and 11) and four lenalidomide doses (5, 10, 15, and 20 mg on days 1 to 14) for a maximum of eight 21-day cycles. For responders, there was an extension, and for patients with progressive disease, dexamethasone (40 mg) was added on the day of and following bortezomib dosing. The MTD was determined to be the dose prior to a level resulting in two or more dose-limiting toxicities.
Of the 38 included patients, 12 had relapsed myeloma and 26 had relapsed and refractory myeloma. They had been treated with a median of five prior therapies; 60% had prior stem cell transplant.
The MTD was declared at lenalidomide 15 mg and bortezomib 1.0 mg/m2. "Very importantly, despite up to 40 cycles of therapy, not a single case of grade 3 or greater peripheral neuropathy occurred," Dr. Richardson said. One case of deep vein thrombosis was reported in a patient receiving lenalidomide alone plus a low-molecular-weight heparin(Drug information on heparin). While there were dose reductions in 16 patients, no patients discontinued therapy.
The overall response rate of 58% included a 6% complete response/near complete response (CR/nCR) rate, a 33% partial response (PR) rate, and a 19% minimal response (MR) rate. "The exciting thing is that these responses were durable at a median of 8 months," Dr. Richardson said. Eleven patients remain on therapy beyond 1 year. Among those patients with progressive disease, for whom dexamethasone was added, some disease stabilization has been reportedPR/MR/SD in 11 of 15 patients (73%).
Dr. Richardson concluded, "We were impressed with the combination of lenalidomide and bortezomib with or without dexamethasone. We are hopeful that this may provide a relatively steroid-sparing approach and that this combination will provide a therapeutic backbone to which other novel agents can be added."