In a nutshell
This study aimed to investigate the maximum tolerated dose of carfilzomib plus melphalan and prednisone (KMP regimen) in patients with newly diagnosed elderly patients with multiple myeloma (MM).
This study concluded that the maximum tolerated dose of carfilzomib was 70mg. Response rates were good in this population.
Some background
Carfilzomib (Kyprolis) is a novel generation proteasome inhibitor. Proteasome inhibitors work by block proteasomes which break down proteins. Cancer cells make large amounts of useless protein. The proteasome inhibitor stops the breakdown of these proteins and allows them to build up. The buildup then kills the cell. Melphalan (Alkeran) is a chemotherapy used for MM. Prednisone (Deltasone) is a treatment used for various cancers. Bortezomib (Velcade) is another commonly used proteasome inhibitor.
It was not known if carfilzomib, melphalan, and prednisone (KMP) would be better than melphalan, prednisone and bortezomib (MPV) standard treatment in elderly patients with newly diagnosed multiple myeloma (eNDMM).
Methods & findings
This study involved 30 patients with eNDMM. Patients received 36, 45, 56 and 70mg of carfilzomib per day on days 1, 8, 15 and 22. They also received melphalan and prednisone. Patients were treated through nine 35-day induction cycles and then received carfilzomib maintenance (treatment given so the cancer does not come back) for 1 year.
Dose-limiting toxicities (DLT) are the side effects of a drug that are serious enough to prevent an increase in the dose of that drug. Low lymphocytes (a type of white blood cells) was a DLT at 36mg. Lysis syndrome (cells killed and contents released into the bloodstream) was a DLT at 45mg. Heart failure and low neutrophils (a type of white blood cells that fight off infections) with fever were DLTs at 56mg. Vomiting and elevated liver enzymes were two DLTs at 70mg.
The overall response rate was 93.3% and 46.6% of patients had a complete response (CR).
The bottom line
This study concluded that the MTD dose of carfilzomib was 70mg. Response rates, and especially CR rate, were very good in elderly patients with newly diagnosed MM.
The fine print
This study had a very small patient population. Further, larger studies are needed.
Published By :
Clinical Cancer Research
Date :
May 03, 2019
