Carfilzomib-Based 3-Drug Regimens for Newly Diagnosed Multiple Myeloma—All That Glitters Is Not Gold

A phase 3 randomized clinical trial (RCT)¹ showing early and deep responses in transplant-eligible and ineligible patients established the role of bortezomib in combination with lenalidomide and dexamethasone (VRd) as standard of care (SOC) therapy for newly diagnosed multiple myeloma (NDMM). Early data showed that the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) in NDMM achieved a very good partial response or better in 81% of the patients.² A phase 2 study established the superiority of carfilzomib and dexamethasone vs lenalidomide and dexamethasone in relapsed/refractory multiple myeloma.³ Similarly, a recently published systematic review of literature⁴ showed early, deep, and durable responses with an acceptable safety profile using KRd in newly diagnosed as well as relapsed/refractory multiple myeloma. However, a phase 3 RCT comparing carfilzomib, melphalan, and prednisone vs bortezomib, melphalan, and prednisone failed to show a meaningful improvement in efficacy regarding the depth and duration of response.⁵