Abstract
Triple class exposed patients with multiple myeloma (MM) represent an unmet need with outcomes remaining poor with those with relapsed/refractory multiple myeloma (RRMM) having a mere 29.8% overall response rate and 12.4-month median overall survival. We explore emerging strategies focusing on bispecific antibodies and CAR-T cell therapies for treatment of refractory myeloma.
Talquetamab (Talq), is a bispecific antibody directed against GPRC5D which has been approved for patients with refractory/relapsed MM who have progressed on at least 4 prior lines of therapy. Patients were treated with Talquetamab as bridge therapy, 77% were treated every 2 weeks and 23% every 4 weeks. Ultimately 119 patients (89%) successfully proceeded to CAR T cell therapy. Teclistamab is the first bispecific antibody designed to redirect T cells by binding CD3 on T-lymphocytes and B-cell maturation antigen (BCMA) on myeloma cells. Most patients who initiated Teclistamab in the outpatient, (54.2%) completed step up dosing using the 3-day dose interval. Elranatamab (PF-06863135) is a humanized bispecific antibody designed to target myeloma cells by simultaneously binding both CD3 receptors T cells and BCMA (on myeloma cells) at which T cells induce a cytotoxic T- cell response. The phase 2 MagnetisMM-3 trial reached its primary endpoint with a confirmed objective response rate (ORR) of 61.0% including complete response of 35%.
The landscape of relapsed/refractory multiple myeloma (RRMM) treatment has been revolutionized by bispecific antibodies and CAR-T cell therapies, offering unprecedented efficacy for heavily pretreated patients.
Keywords
Bispecific antibodies, Chimeric antigen receptor T-cell therapy, Multiple myeloma, Stem cell transplantation