Review Article Details Carfilzomib's Potential in Multiple Myeloma Therapy

Carfilzomib's ability to inhibit myeloma cell growth and ability to trigger a greater response in proteins associated with cell death than other therapies makes it a promising therapy for multiple myeloma patients.

Carfilzomib’s ability to inhibit myeloma cell growth and ability to trigger a greater response in proteins associated with cell death than other therapies makes it a promising therapy for multiple myeloma patients.

Carfilzomib, the latest therapy approved for multiple myeloma, appears to be effective in treating relapsed or refractory forms of the disease, a review article published in the December 2013 edition of Journal of Oncology Pharmacy Practice suggests.

Approved in July 2012 under the brand name Kyprolis, carfilzomib is indicated as a third-line treatment of relapsed or refractory multiple myeloma in patients who have demonstrated disease progression on or within 60 days of completing their last therapy. Most multiple myeloma patients will relapse, eliciting a need for novel cancer therapies, researchers noted.

Carfilzomib binds with the rate-limiting activity involved in breaking down cell proteins; when the process is disabled, the factor that triggers myeloma cell growth remains inactive and the cancer cells do not survive. The inhibition of protein breakdown also leads to cell death, the author added.

In addition, the therapy’s ability to produce a greater response than bortezomib in certain cell proteins that are important to cell death led to research on its ability to counter bortezomib resistance. Despite some cross-resistance, the therapy did produce activity in some resistant cells, the author noted.

After establishing a maximum tolerated dose and an optimal dosing schedule during Phase I and Phase II clinical trials, researchers determined the therapy had an overall response rate of 23.7%, with a median duration of response lasting 7.8 months, and a median overall survival of 15.6 months. In additional Phase I and Phase II trials of carfilzomib with lenalidomide and low-dose dexamethasone, the therapy produced a partial response in 98% of patients after 12 therapy cycles, with 81% of those patients achieving a very good partial response. In addition, 62% of patients achieved a near complete response.

According to the research, the average wholesale price for a 60-mg vial of the therapy is $1658, making the manufacturer’s maximum dosing recommendation per 28-day drug cycle $9948.

In addition to the Phase I and Phase II trials, 3 additional Phase III trials are ongoing and could point to new therapeutic options involving carfilzomib. The trials include a study of lenalidomide, low-dose dexamethasone with or without carfilzomib, a head-to-head trial comparing carfilzomib and low-dose dexamethasone with bortezomib and low-dose dexamethasone, and single-agent carfilzomib in patients with relapsed and refractory multiple myeloma who received 3 prior therapies.