Dr. Davies on the Use of Carfilzomib in Multiple Myeloma

Faith E. Davies, MD, a professor in the Department of Medicine and director of the Clinical Myeloma Program, NYU Langone Health’s Perlmutter Cancer Center, discusses the dosing of carfilzomib (Kyprolis) in the treatment of patients with multiple myeloma.

Carfilzomib is an effective proteasome inhibitor, but one of the issues faced with the agent is that several of the phase III trials investigating its use evaluated different dosing, explains Davies. The original studies examined twice-weekly dosing at 27 mg/m², while other studies have evaluated a 36 mg, a 56 mg, and, more recently, a 70 mg/m² dose.

The ARROW study compared once-weekly dosing of carfilzomib at 70 mg/m2 to twice-weekly dosing at 27 mg/m2 and showed that patients on the once-weekly dosing with the higher dose experienced a better progression-free survival, response rate, and tolerability. These data suggest that using once-weekly dosing, which is more convenient for patients, is also more tolerable, explains Davies.

Carfilzomib has a specific safety profile. Unlike bortezomib, there is not an issue with peripheral neuropathy. However, care needs to be taken when measuring blood pressure, says Davies. There is also potential for shortness of breath with the agent; if that is going to be an issue, it tends to present following the first dose of treatment, according to Davies.

The question of whether the ARROW study data can be taken forward to some combinations remains open, adds Davies. Many of the combination studies have been using twice-weekly dosing of carfilzomib. It may be appropriate to move forward with the once-weekly dosing of the drug, according to Davies, but there are no clinical data to support that approach.