Study Finds It Is Better To Dose Velcade After Melphalan Prior To Stem Cell Transplantation

Results of a recent study suggest that a single dose of Velcade given after high-dose melphalan results in better outcomes in newly diagnosed multiple myeloma patients after stem cell transplantation than a single dose of Velcade given before high-dose melphalan. Side effects of the regimen with Velcade were similar to those seen with melphalan alone.
Treatment with high-dose chemotherapy followed by stem cell transplantion is a standard therapeutic approach for younger, newly diagnosed multiple myeloma patients. High-dose chemotherapy prior to stem cell transplantation, often called a conditioning regimen, is administered with the intention of eliminating cancerous cells from the patient’s bone marrow.
High-dose melphalan (Alkeran), administered as a single dose of 200 mg/m2, is currently the most widely accepted conditioning regimen for multiple myeloma.
According to the study authors, little research has focused on improving the efficacy of the conditioning regimen by combining melphalan with other treatments, which may help improve stem cell transplantation outcomes.
Results from preclinical studies suggest that treatment with melphalan in combination with Velcade (bortezomib) may result in increased myeloma cell death. However, it is not clear if Velcade should be administered before or after melphalan to maximize the synergistic effect of the drugs.
In their study, the researchers sought to determine if the sequence in which Velcade and high-dose melphalan were given before stem cell transplantation affected the efficacy and side effects of the regimen. They also sought to determine the maximum tolerated dose of Velcade that could be administered with high-dose melphalan.
The researchers recruited 39 newly diagnosed multiple myeloma patients who were divided into two treatment groups.
In the first, patients received Velcade treatment 24 hours prior to high-dose melphalan. In the second, patients received Velcade 24 hours after high-dose melphalan was administered.
Within these treatment groups, patients received either 1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2 Velcade, administered in a single dose. These doses were used to determine the maximum tolerated dose that could be administered with melphalan.
Researchers found that of the patients who received Velcade after high-dose melphalan, 55 percent achieved a very good partial response or better within 100 days after the transplant compared to 47 percent of those who received Velcade prior to high-dose melphalan.
Patients who received Velcade after high-dose melphalan had a higher rate of complete response (30 percent) than those treated with Velcade prior to high-dose melphalan (11 percent).
There were no differences in the progression-free survival or the overall survival of patients between treatment groups. For both groups, the overall survival rate was 36.7 months and progression-free survival was 15.3 months.
After conditioning therapy, researchers compared the number of cancerous cells still present in the bone marrow between treatment groups. Although they found that a greater reduction of cancerous cells was achieved whenVelcade was administered after melphalan therapy, results between treatment groups were not found to be statistically different.
Side effects of Velcade and high-dose melphalan were not different or more severe than those seen with high-dose melphalan alone. This was true even for patients who received the highest doses of Velcade.
The study authors suggested that randomized clinical trials be conducted to investigate the efficacy of this regimen compared to melphalan alone.
For more information, please see the study in Clinical Cancer Research (abstract).
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