Immuno-PRISM: A Randomized Phase II Platform Study of Bispecific Antibodies in High-Risk Smoldering Myeloma

Abstract

Background: B-cell Maturation antigen-directed immunotherapies have demonstrated significant efficacy in relapsed and refractory multiple myeloma (RRMM), with recent approval of the bispecific antibody teclistamab (TEC) . However, the use of immunotherapy in high-risk smoldering myeloma (HR-SMM) has not been examined to date. We hypothesized that bispecific antibody therapy would have greater benefit in HR-SMM due to this population having a more intact immune system, lower disease burden and may therefore have a higher efficacy and less toxicity compared to RRMM. Based on previous studies of lenalidomide and dexamethasone demonstrating benefit in HR-SMM, the Immuno-PRISM trial is studying various bispecific antibodies against a control arm of lenalidomide and dexamethasone. Herein, we report our first results of TEC in HR-SMM. Methods: This is a multiple arm, randomized, phase II, platform study evaluating TEC vs lenalidomide and dexamethasone in HR-SMM. Eligibility criteria included HR-SMM per Mayo 2018 “20-2-20” model, total IMWG risk score of 9 or greater, and other previously established high-risk criteria including PETHEMA criteria, evolving-type SMM, and high-risk FISH abnormalities. This study has an initial, safety run-in cohort of 6 patients treated with TEC. All patients receive 2 step-up doses of subcutaneous TEC. In the safety run-in, patients receive a dose lower than the recommended phase 2 dose (RP2D) of TEC. If no dose limiting toxicities (DLTs) are observed,…