Trial reportBritish journal of haematology2016
Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay.
Trial report in British journal of haematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03336073 (Carfilzomib and Dexamethasone in Combination With Cyclophosphamide vs. Carfilzomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma), which is not on this map. Cited by 20 papers.
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.
Carfilzomib and Dexamethasone in Combination With Cyclophosphamide vs. Carfilzomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma: a Phase II Randomized Controlled Trial
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanistic Pharmacokinetic/Pharmacodynamic Modeling in Support of a Patient-Convenient, Longer Dosing Interval for Carfilzomib, a Covalent Inhibitor of the Proteasome.Clinical pharmacokinetics · 2023Trial
- Trial
- Pharmacokinetics, Target Engagement of an Immunoproteasome Subunit Low-Molecular-Mass Polypeptide‑2 (LMP2) Inhibitor AR-01, and Its Anti-Alzheimer's Effects in Rodents.ACS pharmacology & translational science · 2026Article
- Proteasomal inhibition compromises microvascular integrity via distinct effects on non-immune endothelial cells and immune cells.Frontiers in immunology · 2026Article
- Article
- Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation.Science advances · 2023Article
- Zetomipzomib (KZR-616) attenuates lupus in mice via modulation of innate and adaptive immune responses.Frontiers in immunology · 2023Article
- A clinically relevant pulse treatment generates a bortezomib-resistant myeloma cell line that lacks proteasome mutations and is sensitive to Bcl-2 inhibitor venetoclax.Scientific reports · 2022Article
- Site-Specific Proteasome Inhibitors.Biomolecules · 2021Review
- Review
- Proteasome Inhibitors and Their Pharmacokinetics, Pharmacodynamics, and Metabolism.International journal of molecular sciences · 2021Review
- Article
- M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models.Molecular cancer therapeutics · 2021Article
- Recent insights how combined inhibition of immuno/proteasome subunits enables therapeutic efficacy.Genes and immunity · 2020Review
- Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor.Clinical pharmacokinetics · 2019Review
- Positioning of proteasome inhibitors in therapy of solid malignancies.Cancer chemotherapy and pharmacology · 2018Review
- Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome.British journal of pharmacology · 2018Article
- (Immuno)proteasomes as therapeutic target in acute leukemia.Cancer metastasis reviews · 2017Review
- Carfilzomib boosted combination therapy for relapsed multiple myeloma.OncoTargets and therapy · 2017Review
- Polymer micelle formulation for the proteasome inhibitor drug carfilzomib: Anticancer efficacy and pharmacokinetic studies in mice.PloS one · 2017Article
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 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While proteasome inhibition is a validated therapeutic approach for multiple myeloma (MM), inhibition of individual constitutive proteasome (c20S) and immunoproteasome (i20S) subunits has not been fully explored owing to a lack of effective tools. We utilized the novel proteasome constitutive/immunoproteasome subunit enzyme-linked immunosorbent (ProCISE) assay to quantify proteasome subunit occupancy in samples from five phase I/II and II trials before and after treatment with the proteasome inhibitor carfilzomib. Following the first carfilzomib dose (15-56 mg/m(2) ), dose-dependent inhibition of c20S and i20S chymotrypsin-like active sites was observed [whole blood: ≥67%; peripheral blood mononuclear cells (PBMCs): ≥75%]. A similar inhibition profile was observed in bone marrow-derived CD138(+) tumour cells. Carfilzomib-induced proteasome inhibition was durable, with minimal recovery in PBMCs after 24 h but near-complete recovery between cycles. Importantly, the ProCISE assay can be used to quantify occupancy of individual c20S and i20S subunits. We observed a relationship between MM patient response (n = 29), carfilzomib dose and occupancy of multiple i20S subunits, where greater occupancy was associated with an increased likelihood of achieving a clinical response at higher doses. ProCISE represents a new tool for measuring proteasome inhibitor activity in clinical trials and relating drug action to patient outcomes.
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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.