ArticleNature medicine2023
Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma.
Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 240 papers, 6 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
240 citing papers in PubMed, 6 syntheses or guidelines pooled it, 284 citations in OpenAlex.
- T-cell-redirecting therapies in early relapsed multiple myeloma: a systematic review and network meta-analysis.Journal of hematology & oncology · 2026Pooled it
- T-Cell Engagers TargetingInternational journal of molecular sciences · 2026Pooled it
- Global development of bispecific antibodies in oncology: a bibliometric analysis of geographic disparities, collaborative models, and emerging translational strategies.Frontiers in immunology · 2026Pooled it
- Efficacy and safety of CD38-directed CAR-T cell therapy for multiple myeloma: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- A Systematic Review and Meta-analysis on the Safety and Efficacy of CAR T Cell Therapy Targeting GPRC5D in Patients with Multiple Myeloma: A New Insight in Cancer Immunotherapy.Anti-cancer agents in medicinal chemistry · 2025Pooled it
- Efficacy and safety of teclistamab in relapsed or refractory multiple myeloma: a systematic review and meta-analysis.Annals of hematology · 2024Pooled it
- Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial.Nature medicine · 2026Trial
- Trial
- Trial
- CAR-T-centered sequential therapy: current status, challenges, and future clinical perspectives.Journal of hematology & oncology · 2026Review
- Bispecific antibodies are becoming the preferred standard of care in relapsed/refractory multiple myeloma.Blood advances · 2026Article
- Distinct epitope engagement confers differential activity of linvoseltamab vs teclistamab across BCMA mutations.Blood advances · 2026Article
- Next-generation immune cell engagers for B cell depletion in autoimmune diseases.Nature reviews. Drug discovery · 2026Review
- Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma.Nature medicine · 2026Article
- Patient-Specific Determinants of Response to BCMA- and GPRC5D-Targeted CAR T-Cell Therapy in Multiple Myeloma: A QSP Analysis of Clinical Trial and Real-World Data.Clinical pharmacology and therapeutics · 2026Article
- Dual targeting of BCMA and GPRC5D with the trispecific antibody ramantamig addresses antigenic heterogeneity in myeloma.HemaSphere · 2026Article
- Early deep response to cilta-cel as 2nd CAR T-Cell therapy after CELMoD-based bridging for advanced multiple myeloma.Annals of hematology · 2026Article
- A single-arm prospective phase I trial of 68Ga-PFBC01 PET/CT for multiple myeloma B cell maturation antigen imaging.The Journal of clinical investigation · 2026Article
- Imaging B cell maturation antigen in multiple myeloma.The Journal of clinical investigation · 2026Article
- TNFRSF17 genomic profiling guides retreatment with alternative BCMA-directed immunotherapies in multiple myeloma.Blood advances · 2026Article
180 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 9 institutions in 3 countries.
Funding
Abstract
B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy. In two cases, MM relapse post-TCE/CAR T therapy was driven by BCMA-negative clones harboring focal biallelic deletions at the TNFRSF17 locus at relapse or by selective expansion of pre-existing subclones with biallelic TNFRSF17 loss. In another five cases of relapse, newly detected, nontruncating, missense mutations or in-frame deletions in the extracellular domain of BCMA negated the efficacies of anti-BCMA TCE therapies, despite detectable surface BCMA protein expression. In the present study, we also report four cases of MM relapse with biallelic mutations of GPRC5D after anti-GPRC5D TCE therapy, including two cases with convergent evolution where multiple subclones lost GPRC5D through somatic events. Immunoselection of BCMA- or GPRC5D-negative or mutant clones is an important tumor-intrinsic driver of relapse post-targeted therapies. Mutational events on BCMA confer distinct sensitivities toward different anti-BCMA therapies, underscoring the importance of considering the tumor antigen landscape for optimal design and selection of targeted immunotherapies in MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.