The emerging role of carfilzomib combination therapy in the management of multiple myeloma.

Carfilzomib is a proteasome inhibitor that selectively and irreversibly binds to its target, resulting in sustained inhibition absent of off-target effects relative to bortezomib. Single-agent carfilzomib has produced robust and durable responses in clinical trials and it has been approved in the US for treating relapsed and refractory multiple myeloma (MM). Due to its favorable safety profile, carfilzomib is particularly suitable for use in combination strategies. Promising data have been reported from studies that investigated the use of carfilzomib in combination with immunomodulators, alkylating agents, glucocorticoids, histone deacetylase inhibitors and kinesin spindle protein inhibitors. Ongoing pivotal randomized Phase III studies are investigating the efficacy and safety of carfilzomib combinations in patients with relapsed MM and transplant ineligible patients.