The treatment of relapsed multiple myeloma remains challenging. Based on interim data from the randomized Phase III IKEMA study demonstrating a progression-free survival benefit with a combination of isatuximab (Isa, a CD38-targeted monoclonal antibody) and carfilzomib/dexamethasone (Kd) versus Kd alone, Isa-Kd recently received regulatory approval in the USA and Europe for patients with multiple myeloma who have received at least one prior line of therapy (in the USA, up to three prior lines). In this review we discuss the rationale and clinical trial experience to date with Isa-Kd. Although final IKEMA results are pending, Isa-Kd has emerged as an effective and tolerable therapy for patients with relapsed multiple myeloma. Given the growing number of antibody-containing triplet regimens in this setting, potential niches and limitations for Isa-Kd are also discussed.
Keywords: carfilzomib; isatuximab; monoclonal antibodies; multiple myeloma.
Lay abstract For patients with multiple myeloma, navigating cancer relapses can be difficult. The combination of isatuximab, carfilzomib and dexamethasone (Isa-Kd), which was studied in the large ongoing IKEMA study, has recently been approved by government authorities in both the USA and Europe for treating multiple myeloma that has relapsed after initial therapy. Isatuximab is a drug that attacks the CD38 protein on myeloma cancer cells, while carfilzomib is a drug that prevents myeloma cancer cells from properly using and reusing proteins. Dexamethasone is a corticosteroid that has been shown to improve how well other antimyeloma drugs work. In this review, we discuss potential strengths and weaknesses of the Isa-Kd combination for patients with multiple myeloma that has relapsed.