ArticleBlood2019
γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03502577 (A Phase I Study of B-Cell Maturation Antigen), which is not on this map. Cited by 215 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase I Study of B-Cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T Cells in Combination With JSMD194, a Small Molecule Inhibitor of Gamma Secretase, in Patients With Relapsed or Persistent Multiple Myeloma
Who cites it
215 citing papers in PubMed, 2 syntheses or guidelines pooled it, 314 citations in OpenAlex.
- Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.Frontiers in pharmacology · 2023Pooled it
- B-cell maturation antigen expression across hematologic cancers: a systematic literature review.Blood cancer journal · 2020Pooled it
- Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial.Nature communications · 2024Trial
- A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma.Gene therapy · 2021Trial
- Elranatamab: A novel B-cell maturation T-cell engager.Human vaccines & immunotherapeutics · 2026Review
- The NFIL3-MYC signaling axis: a novel therapeutic target and prognostic marker in high-risk multiple myeloma.Biomarker research · 2026Article
- Imaging B cell maturation antigen in multiple myeloma.The Journal of clinical investigation · 2026Article
- APRIL-driven BCMA/TACI dual-targeted ligand-drug conjugates for selective and potent therapy of multiple myeloma.Acta pharmaceutica Sinica. B · 2026Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- Integrated transcriptomics reveals a TNFRSF-metabolism axis and a context-dependent BCMA signaling state in myeloma progression.Annals of hematology · 2026Article
- Enhanced BCMA Antigen Density Increases Trogocytosis and Attenuates CAR T cell Function.bioRxiv : the preprint server for biology · 2026Article
- Navigating the Therapeutic Landscape of Multiple Myeloma: Immunotherapy, Microenvironment, and Resistance.Biomedicines · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Engineering Soluble Recombinant BCMA for Ide-Cel Labeling.European journal of immunology · 2026Article
- Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy.Blood cancer journal · 2026Article
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- CC-DenseSTORM: deep learning enables colorimetry camera-based simultaneous two-color single-molecule localization microscopy with dense emitters.Biomedical optics express · 2026Article
- Review
155 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
B-cell maturation antigen (BCMA) is a validated target for chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM). Despite promising objective response rates, most patients relapse, and low levels of BCMA on a subset of tumor cells has been suggested as a probable escape mechanism. BCMA is actively cleaved from the tumor cell surface by the ubiquitous multisubunit γ-secretase (GS) complex, which reduces ligand density on tumor cells for CAR T-cell recognition and releases a soluble BCMA (sBCMA) fragment capable of inhibiting CAR T-cell function. Sufficient sBCMA can accumulate in the bone marrow of MM patients to inhibit CAR T-cell recognition of tumor cells, and potentially limit efficacy of BCMA-directed adoptive T-cell therapy. We investigated whether blocking BCMA cleavage by small-molecule GS inhibitors (GSIs) could augment BCMA-targeted CAR T-cell therapy. We found that exposure of myeloma cell lines and patient tumor samples to GSIs markedly increased surface BCMA levels in a dose-dependent fashion, concurrently decreased sBCMA concentrations, and improved tumor recognition by CAR T cells in vitro. GSI treatment of MM tumor-bearing NOD/SCID/γc-/- mice increased BCMA expression on tumor cells, decreased sBCMA in peripheral blood, and improved antitumor efficacy of BCMA-targeted CAR T-cell therapy. Importantly, short-term GSI administration to MM patients markedly increases the percentage of BCMA+ tumor cells, and the levels of BCMA surface expression in vivo. Based on these data, a US Food and Drug Administration (FDA)-approved clinical trial has been initiated, combining GSI with concurrent BCMA CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT03502577.
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Identifiers
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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.