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2024-04-09T14:51:50.000Z

Symposium | Beyond BCMA: Novel strategies using bispecific antibodies

Apr 9, 2024
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Learning objective: After reading this article, learners will be able to describe novel therapeutic targets in MM and explain the mechanisms of action for new agents in MM.

Test your knowledge! Take our quick quiz before and after you read this article to find out if you improved your knowledge. Results help us to improve content and continually provide open-access education.

During the Multiple Myeloma Hub virtual symposium held on March 11, 2024, “Current and future perspectives for bispecific antibodies in multiple myeloma: Learnings from 2023,” Amrita Krishnan, City of Hope Comprehensive Cancer Center, Duarte, US, delivered a presentation on novel strategies using bispecific antibodies beyond B-cell maturation antigen (BCMA)-directed therapies.

Krishnan discussed alternative targets for bispecific antibodies on myeloma cells, including G-protein coupled receptor family C group 5 member D (GPRC5D) and Fc receptor-homolog 5 (FcRH5), touching on a new development in dual-targeting trispecific antibodies (Figure 1). Krishnan presented clinical data from approved and investigational non-BCMA targeting agents, as well as highlighting the optimal sequencing in the myeloma treatment paradigm (Figure 2).

Figure 1. Mechanism of action of JNJ-79635322, a potential first-in-class trispecific antibody targeting BCMA, GPRC5D, and CD3 

BCMA, B-cell maturation antigen; GPRC5D, G protein–coupled receptor family C group 5 member D; IFN-γ, interferon-gamma; IgG, immunoglobulin G; IL, interleukin; MM, multiple myeloma; TNF, tumor necrosis factor.
*Adapted from Pillarisetti, et al.1

 

Figure 2. Response rates with CAR T-cell and subsequent therapy after talquetamab in the MonumenTAL-1 trial* 

BsAb, bispecific antibody; CAR, chimeric antigen receptor; CR, complete response; GPRC5D, G protein–coupled receptor, class C group 5 member D; IMiD, immunomodulatory agent;  mAb, monoclonal antibody; ORR, overall response rate; PI, proteosome inhibitor; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
*Data from Sanchez.2

This independent medical activity was funded by Janssen and Bristol Myers Squibb. All content was developed independently by the faculty. The funders were allowed no influence on the content of this activity.

  1. Pillarsetti K, Edavettal S, Mendonca M, et al. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020;135(15):1232-1243. DOI: 1182/blood.2019003342.
  2. Sanchez L, Schinke C, Krishnan A, et al. Clinical outcomes of subsequent therapies in patients with relapsed/refractory multiple myeloma following talquetamab treatment: analyses from the phase 1/2 MonumenTAL-1 study. Blood. 2023;142 (Suppl.1):2007. DOI: 1182/blood-2023-182330

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