The FDA on July 20, 2012 granted accelerated approval to KYPROLIS® for the treatment of patients with multiple myeloma who have received at least two prior therapies, including VELCADE® (Bortezomib) and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of the last therapy. KYPROLIS® is a product of Onyx Pharmaceuticals.
Tag: Multiple Myeloma
PX-171-003-A1, an open-label, single-arm, phase (Ph) II study of carfilzomib (CFZ) in patients (pts) with relapsed and refractory multiple myeloma (R/R MM) Long-term follow-up and subgroup analysis
SUMMARY: KYPROLIS® (Carfilzomib) is a second generation proteasome inhibitor. Unlike VELCADE® (Bortezomib), proteasome inhibition with KYPROLIS® is irreversible. The approval of KYPROLIS® was based on a phase 2b, single-arm, multicenter clinical study in which 266 patients with advanced refractory Multiple Myeloma who had progressed on 2 or more prior therapies were evaluated. Prior therapies included treatment with VELCADE® (Bortezomib), REVLIMID® (Lenalidomide) or THALOMID® (Thalidomide). The primary end point was Overall Response Rate (ORR). The ORR with single agent KYPROLIS® was 24%, with a median duration of response of 7.4 months. This benefit was seen regardless of unfavorable cytogenetics. Peripheral neuropathy was infrequent and the most common adverse events were primarily hematologic. Patients with resistant and refractory Multiple Myeloma now have a new treatment option after a six year hiatus. Siegel DSD, Martin T, Wang M, et al. J Clin Oncol 29: 2011 (suppl; abstr 8027)
Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma
SUMMARY: REVLIMID® (Lenalidomide) is an immunomodulatory agent with significant activity in patients with Multiple Myeloma, by virtue of its multiple mechanism of action. In this randomized, double blind, multicenter study, patients 65 years or older with newly diagnosed multiple myeloma, ineligible for transplantation, were randomized and the comparison was MPR followed by R (melphalan, prednisone and REVLIMID® followed by REVLIMID® maintenance) vs MPR or MP followed by placebo. There was a statistically significant prolongation in the progression free survival with a 51% reduction in the risk of progression for those who received REVLIMID® maintenance (MPR followed by R) compared to those who received MPR followed by placebo. This benefit was predominantly observed in patients who were 65-75 years of age. The response rates were also higher in the MPR-R and MPR groups compared to the MP group. There was a slightly higher incidence of second primary malignancies in those exposed to REVLIMID® (MPR-R and MPR) compared to the MP group (7% vs 3%). This study has demonstrated the benefit of adding REVLIMID® for induction therapy as well as maintenance, in patients 65-75 years of age, ineligible for transplant. Palumbo A, Hajek R, Delforge M, et al. N Engl J Med 2012;366:1759-1769
Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma
SUMMARY: REVLIMID® (Lenalidomide) is an immunomodulatory agent with significant activity in patients with Multiple Myeloma, by virtue of its multiple mechanisms of action. In two, double blind, randomized, phase III trials, patients with stable disease following stem cell transplantation, were randomized to receive either REVLIMID® (Lenalidomide) or placebo maintenance, until progression. In both these studies there was a statistically significant improvement in the progression free survival or time to progression in the patient group receiving REVLIMID® maintenance. This benefit was independent of response to initial induction therapy at the time of randomization and other patient characteristics such as B2 microglobulin, cytogenetics or exposure to lenalidomide or thalidomide during induction. There was however a slightly higher incidence of second primary malignancies in the REVLIMID® group compared to the placebo group (8% vs 4%). We have come a long way, controlling this disease and maintenance REVLIMID® has paved the way, changing Multiple Myeloma into a chronic disease. McCarthy PL, Owzar K, Hofmeister CC, et al. N Engl J Med 2012;366:1770-1781 and Attal M, Lauwers-Cances V, Marit G, et al. N Engl J Med 2012;366:1782-1791