Carfilzomib promising for multiple myeloma31 Jan 2016
The use of regimens containing carfilzomib (Kyprolis) for the treatment of relapsed and/or refractory multiple myeloma (RR-MM) in patients previously exposed to bortezomib (Velcade) and lenalidomide (Revlimid) yielded an overall response rate of 47.2% with manageable toxicity, a retrospective multicenter study has shown.
The optimal combination has yet to be determined
Predictors of response included refractoriness to bortezomib and to lenalidomide, said researchers. The number of prior lines of therapy also had an impact on response rate, as did albumin <35 g/L, according to Eli Muchtar, MD, of the Rabin Medical Centre in Petah Tikva, Israel, and colleagues.
"This study provides important data on predictors of response to carfilzomib and supports combination treatment to improve response, although the optimal combination has yet to be determined," the investigators reported. "As drug resistance is an important factor in determining response quality to carfilzomib in this study, a better understanding of the resistance mechanism(s) can help in both treatment selection as well as in creating ways to overcome it."
The study included “real-life” patients
The study looked at 135 patients with RR-MM at 10 medical centers in Israel. All received carfilzomib-containing salvage therapy outside of a clinical trial between March 2013 and April 2015. The median age at carfilzomib initiation was 67.9 years (range 41-88) and there was an equal balance of male and female patients.
All had previously been treated with both bortezomib and at least one immunomodulatory drug and there was no restriction on patient inclusion, said the investigators. "Thus, our cohort of patients represents 'real life' patients and not a pre-selected population, as in clinical trials," they said.
Carfilzomib was given by intravenous infusion over 10-30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. The recommended dose of carfilzomib was 20 mg/m2 on days 1 and 2 of cycle 1. If this was well-tolerated, the dose was increased to 27 mg/m2.
“Increase of the dose did not result in a better outcome”
Although this schedule yielded the best overall response rate in this study, further increase of the dose did not result in a better outcome, noted the investigators. "It might be that combination treatment and not dose intensification is currently the only practical method to improve the response rate in this group of patients," they said.
The median duration of response was 8.4 months, and was significantly higher in patients receiving a three-drug combination rather than a two-drug regimen or carfilzomib alone. "This holds promise for additional improvements with combination regimens, as the drugs that were used in the combination regimens, besides carfilzomib, were mainly glucocorticoids and alkylators," said Muchtar and colleagues. In addition:
- The median progression-free survival and overall survival for the entire cohort was 4.9 months, respectively.
- Patients who achieved a partial response or better received a mean of 3 prior lines compared to 36 prior lines in those who failed to achieve a response, said the investigators.
- Treatment-related death was seen in 5.2% of patients, a rate higher than that reported in carfilzomib clinical trials.