Clinical Report: Ramantamig Targets BCMA and GPRC5D in Multiple Myeloma
Overview
The supplied article describes preclinical evaluation of ramantamig, a trispecific antibody that engages CD3 on T cells and targets BCMA and GPRC5D on multiple myeloma (MM) cells. The study assessed activity in cell lines and in 32 patient bone-marrow samples with variable target expression; the provided material does not include the results of those assays.
Background
Despite substantial survival improvements in MM, patients whose disease is resistant to immunomodulatory drugs, proteasome inhibitors, and CD38-targeting antibodies have a poor prognosis. Bispecific antibodies targeting BCMA or GPRC5D have shown overall response rates of 60%–70% and median progression-free survival of approximately 11–17 months in heavily pretreated patients, but responses are not universal and relapse occurs. Variation in target expression and genetic or epigenetic target inactivation, termed antigen escape, are described as potential contributors to treatment resistance. Ramantamig was studied as a trispecific approach engaging T-cell CD3 while targeting both BCMA and GPRC5D on MM cells.
Data Highlights
Measure or study feature
Source-reported information
Response rates with BCMA- or GPRC5D-targeting bispecific antibodies in heavily pretreated MM
60%–70%
Median progression-free survival reported for these bispecific antibodies
Approximately 11–17 months
Patient bone-marrow samples evaluated for ex vivo ramantamig efficacy
32 samples; samples required at least 1% MM cells and sufficient material
Ramantamig targets
CD3 on T cells and BCMA and GPRC5D on MM cells
Cell-line assessment
MM cell lines, including a BCMA-knockout MM.1S line, were used in preclinical evaluation
Key Findings
BCMA is expressed by B cells, plasma cells, and malignant plasma cells and supports plasma-cell and MM-cell survival.
GPRC5D is highly expressed on MM cells, has substantially lower expression in normal plasma cells, and is restricted to keratin-producing cells in normal tissues, according to the supplied article.
Expression levels of BCMA and GPRC5D vary among MM cells, and the article identifies this heterogeneity as a possible contributor to variable responses.
Genetic or epigenetic inactivation of BCMA or GPRC5D has been reported in patients relapsing during target-directed bispecific-antibody therapy; the article refers to this as antigen escape.
The study evaluated ramantamig against MM cell lines using healthy-donor T cells and in 32 patient bone-marrow samples using autologous T cells and primary MM cells with variable BCMA and GPRC5D expression.
The supplied article excerpt describes the study rationale and methods but does not provide assay results or clinical outcomes for ramantamig.
Clinical Implications
The supplied material supports describing ramantamig as a preclinical dual-antigen-targeting strategy designed to engage CD3-positive T cells and MM cells expressing BCMA and/or GPRC5D. It does not provide efficacy or safety results sufficient to draw conclusions about clinical benefit or use in patients.
Conclusion
Ramantamig was evaluated as a trispecific approach to address variable BCMA and GPRC5D expression in MM. The provided source excerpt does not report the study’s experimental outcomes, so its activity cannot be summarized from this material.
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
