ArticleBlood cancer journal2019
Phase I study of the anti-FcRH5 antibody-drug conjugate DFRF4539A in relapsed or refractory multiple myeloma.
Article in Blood cancer journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Dawn of a new era of antibody-drug conjugates and bispecific T-cell engagers for treatment of multiple myeloma: a systematic review of literature.Annals of hematology · 2021Pooled it
- Therapeutic outcome of early-phase clinical trials in multiple myeloma: a meta-analysis.Blood cancer journal · 2021Pooled it
- Interim PET response of Pola-R-CHP predicts outcome in previously untreated CD5-positive diffuse large B-cell lymphoma: a multicenter retrospective study.Annals of medicine · 2026Article
- Structure-function analysis of the FCRL5-IgG1 Fc complex reveals an unappreciated pathway for B cell modulation by Fc-attenuated IgG.Science advances · 2026Article
- FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial.Nature medicine · 2026Article
- Structure-Function Analysis of the FCRL5-IgG1 Fc Complex Reveals an Unappreciated Effect of Fc-Silent Antibodies on B cells.bioRxiv : the preprint server for biology · 2026Article
- Human FcRL5 is an Fc receptor that simultaneously engages two IgGs.Science advances · 2026Article
- High FCRL5 expression predicts poor treatment response and survival in newly diagnosed multiple myeloma: a retrospective study.Frontiers in oncology · 2026Article
- T cell redirecting therapy for relapsed multiple myeloma.Discover oncology · 2025Review
- Management of Toxicities Associated with BCMA, GPRC5D, and FcRH5-Targeting Bispecific Antibodies in Multiple Myeloma.Current hematologic malignancy reports · 2024Review
- Are we there yet? CAR-T therapy in multiple myeloma.British journal of haematology · 2024Review
- Bispecific antibodies in the treatment of multiple myeloma.Blood cancer journal · 2024Review
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Multiple myeloma: signaling pathways and targeted therapy.Molecular biomedicine · 2024Review
- Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Fc receptor-like 5 (FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma.Signal transduction and targeted therapy · 2024Article
- Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma.Nature communications · 2023Article
- Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma.Cancer research · 2023Article
- FCRL1 immunoregulation in B cell development and malignancy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 1 country.
Funding
Abstract
FcRH5 is a cell surface marker enriched on malignant plasma cells when compared to other hematologic malignancies and normal tissues. DFRF4539A is an anti-FcRH5 antibody-drug conjugated to monomethyl auristatin E (MMAE), a potent anti-mitotic agent. This phase I study assessed safety, tolerability, maximum tolerated dose (MTD), anti-tumor activity, and pharmacokinetics of DFRF4539A in patients with relapsed/refractory multiple myeloma. DFRF4539A was administered at 0.3-2.4 mg/kg every 3 weeks or 0.8-1.1 mg/kg weekly as a single-agent by intravenous infusion to 39 patients. Exposure of total antibody and antibody-conjugate-MMAE analytes was linear across the doses tested. There were 37 (95%) adverse events (AEs), 8 (21%) serious AEs, and 15 (39%) AEs ≥ grade 3. Anemia (n = 10, 26%) was the most common AE considered related to DFRF4539A. Two cases of grade 3 acute renal failure were attributed to DFRF4539A. There were no deaths; the MTD was not reached. DFRF4539A demonstrated limited activity in patients at the doses tested with 2 (5%) partial response, 1 (3%) minimal response, 18 (46%) stable disease, and 16 (41%) progressive disease. FcRH5 was confirmed to be expressed and occupied by antibody post-treatment and thus remains a valid myeloma target. Nevertheless, this MMAE-based antibody-drug-conjugate targeting FcRH5 was unsuccessful for myeloma.
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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.