Ramantamig’s trispecific targeting of BCMA and GPRC5D may overcome antigen heterogeneity in multiple myeloma

By
Chloe O'Neill
Marloes E. C. Broekmans
Charlotte L. B. M. Korst
Maria Krevvata
Giada Dal Collo
Richard W. Groen
Bing Li
Serena R. Baglio
Ulrike Philippar
Kodandaram Pillarisetti
Sonja Zweegman
Deeksha Vishwamitra
Tuna Mutis
Niels W. C. J. van de Donk
October 7, 2026

Hemasphere

Objective:

To assess preclinical anti-myeloma activity of ramantamig, which engages CD3 on T cells and targets BCMA and GPRC5D on myeloma cells, including in samples with variable target expression.

Approach:

Cell-line assays: Tested ramantamig against luciferase-transduced myeloma cell lines, including a BCMA-knockout line, using healthy-donor peripheral blood mononuclear cells as effectors.
Patient-sample assays: Measured 48-hour ex vivo lysis in bone marrow samples from 32 patients using autologous cells; samples contained 1%–68% myeloma cells (median 15%).
Comparators and activity measures: Compared ramantamig with single-target and control antibodies; assessed myeloma-cell survival and T-cell activation and degranulation.

Key Findings:

The supplied article context describes the study design but does not report assay results.

Interpretation:

The provided material establishes the rationale and methods for evaluating dual BCMA/GPRC5D targeting in the setting of variable antigen expression; it does not provide findings to determine whether ramantamig overcame antigen heterogeneity.

Limitations:

The supplied context ends during the methods and contains no results or discussion.
Ex vivo testing was limited to bone marrow samples with at least 1% myeloma cells and sufficient material.