Bispecific T-cell engager therapy for multiple myeloma

Abstract

With upfront use of triplet- and quadruplet-based regimens coupled with autologous stem cell transplant (ASCT) and maintenance lenalidomide, a high proportion of multiple myeloma (MM) patients are achieving deep and durable responses. Yet, myeloma invariably relapses, with refractoriness to one or more drugs at first relapse. This therapeutic gap has been partially filled by T-cell engager (TCE) therapies that have demonstrated remarkable response rates and prolonged remissions in heavily pretreated patients with MM, providing off-the-shelf immunotherapy options leading to the U.S. Food and Drug Administration (FDA) approval of three bispecific TCEs teclistamab, elranatamab, and talquetamab. We review the most salient aspects of TCE design and clinical experience in MM treatment. Combination approaches overcome resistance mechanisms, while earlier TCE use could enhance depth and durability of response. Outpatient step-up dosing (SUD) further enables community adoption.

Keywords: BCMA; Bispecifics; GPRC5D; Immunotherapy; Myeloma; T-cell engagers.