Future of R/R MM: Emerging Bispecifics and Trispecifics
Panelists discuss how the emerging trispecific antibody (targeting both T cells and natural killer [NK] cells) has generated significant excitement with its unprecedented 100% overall response rate in B-cell maturation antigen (BCMA)–exposed patients, while incorporating lessons learned from earlier bispecifics such as starting with Q4 weekly dosing and built-in tocilizumab prophylaxis, although they acknowledge this breakthrough may completely reshape treatment sequencing strategies and create new challenges in determining optimal therapy combinations.
EP: 1.MonumenTAL-1: Outcomes From the Extended Median Follow-Up Data
EP: 2.MonumenTAL-1: Outcomes From the Extended Median Follow-Up Data (Part 2)
EP: 3.Data Review of Teclistamab and Elranatamab in R/R MM
EP: 4.Expert Opinion on Modern Availability of Several Agents
EP: 5.Future of R/R MM: Emerging Bispecifics and Trispecifics
EP: 6.Optimal Dosing of Talquetamab
Future of Relapsed/Refractory Multiple Myeloma (R/R MM): Emerging Bispecifics and Trispecifics
The trispecific antibody targeting both T cells and NK cells has generated significant excitement in the multiple myeloma community, particularly following presentations at recent medical meetings. This innovative approach addresses potential resistance mechanisms by engaging 2 different immune cell populations simultaneously. Early data show remarkable efficacy with an overall response rate of 86% in the general population, but most notably achieved a 100% response rate in patients without prior BCMA exposure, representing an unprecedented level of activity that mirrors chimeric antigen receptor T-cell therapy responses but in an off-the-shelf format.
The trispecific demonstrates several potential advantages over current bispecific therapies, including a more favorable safety profile with lower cytokine release syndrome rates (30%, predominantly grade 1) and the ability to initiate treatment with monthly dosing from the start. The manufacturer appears to be incorporating lessons learned from earlier bispecific experiences, with the registration trial designed to use every-4-week dosing and immediate incorporation of tocilizumab prophylaxis. These features could significantly improve treatment convenience and accessibility, potentially facilitating broader adoption in outpatient settings where most patients with myeloma receive care before referral to academic centers.
The emergence of trispecific therapy is poised to disrupt current treatment paradigms and sequencing strategies in multiple myeloma. Although the depth of responses is impressive, longer follow-up data are needed to assess durability and overall survival outcomes. The introduction of this therapy raises important questions about optimal treatment sequencing, particularly regarding whether patients who receive trispecific therapy can subsequently benefit from BCMA-targeted bispecifics or GPRC5D-targeted agents. These sequencing questions will likely be answered through real-world experience as this technology advances. The rapid evolution of the myeloma treatment landscape continues to challenge practitioners to adapt their therapeutic strategies and remain current with emerging options.
