VELCADE(R) (Bortezomib) for Injection Addressed Disease-Related Complications Associated with Multiple Myeloma
Thursday June 28, 12:00 pm ET
- Promoted bone growth in patients with bone degeneration -
- Improved overall survival for broad patient population including those with reduced renal function -
KOS, Greece, June 28 2007 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - News) today reported on data presentations of VELCADE that showed improved outcomes for multiple myeloma (MM) patients affected by bone degeneration and renal impairment. MM is a plasma cell disease and carries significant risk of bone erosion and skeletal compromise. In addition, kidney function frequently is impaired. Approximately 50 percent of patients will experience renal dysfunction in the course of their disease. The clinical findings were presented at the prestigious 11th International Myeloma Workshop (IMW) in Kos, Greece. Highlights included:
-- In patients affected by MM-related bone degeneration, VELCADE and dexamethasone combination therapy demonstrated an increase in biomarkers indicative of bone formation. These results validate findings from a previously presented study, which measured actual patient biopsies for improvement in bone volume and thickness and found that VELCADE promoted bone growth.
-- In a retrospective analysis of a clinical trial, VELCADE showed comparable positive median overall survival (OS) and overall response rate (ORR) in patients both with renal impairment and those with normal renal function. In a supporting study of MM patients with increased biomarker levels indicating poor renal function and poor survival prognosis, VELCADE produced a high ORR and improved renal function.
"VELCADE not only demonstrates a survival benefit for previously treated multiple myeloma patients, but also it can be used in patients with common disease-related complications, such as bone degeneration and renal impairment. VELCADE is the only agent that has shown this consistently and does not require dose modifications," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "These data further underscore the need to use VELCADE broadly, offering comprehensive care for patients."
VELCADE Plus Dexamethasone Therapy Induces Osteoblast Activation in Responsive Patients with Multiple Myeloma (Abstract #PO-311)
The Phase II trial assessed bone metabolism and efficacy of VELCADE and dexamethasone combination therapy in patients with relapsed / refractory MM. The study enrolled 14 patients who received VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Patients also received 20 mg of dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12. Results were presented by Shuji Ozaki, M.D., The University of Tokushima Graduate School of Health Biosciences, and showed an ORR (very good partial response + partial response) of 71 percent. A rapid increase of serum alkaline phosphatase (ALP) was observed in treatment-responsive patients. Bone formation markers such as serum bone specific ALP and osteocalcin significantly increased in six and three patients, respectively. Additionally, a radiographic examination showed fewer bone lesions. These findings suggest that VELCADE based therapy induced osteoblast activation. Side effects were manageable, including thrombocytopenia, peripheral neuropathy and ileus.
These results support a previous study presented by Maurizio Zangari, M.D., University of Arkansas for Medical Sciences, at the 2007 European Hematology Association meeting. In the study of 10 evaluable relapsed / refractory MM patients, VELCADE was administered at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Patients were treated for three cycles. Bone biopsies were obtained at baseline and, after treatment, measured bone volume / total volume in trabecular thickness by micro-computed tomography. Bone formation also was determined by histomorphometry. Results showed an increase in bone volume equal to or greater than 40 percent from baseline in four out of five patients after just 12 weeks of therapy. A parallel increase in trabecular thickness also was observed, showing a positive skeletal response to the therapy.
VELCADE in Renally Impaired Multiple Myeloma Patients (Abstract #PO-1114)
The retrospective analysis of the APEX Phase III study assessed VELCADE efficacy and safety in patients with varying degrees of renal impairment. The APEX trial had compared VELCADE to high-dose dexamethasone in MM patients, who had received one to three prior therapies, and showed 29.8 months median OS for patients on VELCADE, a six-month benefit over high-dose dexamethasone. The retrospective analysis included data from 313 evaluable patients. Response rate, time to progression (TTP) and OS were analyzed in four sub- groups of patients, ranging from severe to no renal impairment as classified by creatinine clearance levels. Results were presented by Jesus San Miguel, M.D., Ph.D., Hospital Universitario de Salamanca, and showed that response rate, TTP and OS for patients on VELCADE were similarly positive across all four patient sub-groups. Time to response was rapid, which is the goal of treatment for patients with renal impairment. Given the survival benefit seen in these patients, VELCADE may overcome poor prognosis associated with renal impairment. Adverse events, discontinuations and dose reductions also were similar across all four patient sub-groups.
Cystatin-C: an Early Marker of Renal Impairment and an Independent Predictive Factor for Survival in Multiple Myeloma. Reduction Post-VELCADE Therapy (Abstract #PO-227)
The Phase II study was designed not only to evaluate the impact of VELCADE on serum levels of Cystatin-C, an early biomarker for poor renal function, but also to explore possible correlations with clinical response, including survival. Impaired renal function is known to be an indicator of poor survival prognosis. The study included 155 MM patients who were treated with VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Results were presented by Evangelos Terpos, M.D., General Airforce Hospital, and showed that VELCADE reduced Cystatin-C levels, demonstrating effectiveness in patients with decreased renal function, and the potential ability to improve survival in these patients. |
