Exceptional Response to Bromodomain and Extraterminal Domain Inhibitor Therapy With BMS-986158 in <i>BRD4-NUTM1</i> NUT Carcinoma Harboring a <i>BRD4</i> Splice Site Mutation
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Abstract
Article Tools CASE REPORTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/PO.22.00633 JCO Precision Oncology no. 7 (2023) e2200633. Published online June 29, 2023. PMID: 37384867 Exceptional Response to Bromodomain and Extraterminal Domain Inhibitor Therapy With BMS-986158 in BRD4-NUTM1 NUT Carcinoma Harboring a BRD4 Splice Site Mutation Michael L. Cheng , MD1,2xMichael L. ChengSearch for articles by this author; Yeying Huang, BS3xYeying HuangSearch for articles by this author; Nhi Luong, BS3xNhi LuongSearch for articles by this author; Jaclyn LoPiccolo, MD1,2xJaclyn LoPiccoloSearch for articles by this author; Mizuki Nishino , MD, MPH4,5xMizuki NishinoSearch for articles by this author; Lynette M. Sholl , MD3xLynette M. ShollSearch for articles by this author; Lucian R. Chirieac , MD3xLucian R. ChirieacSearch for articles by this author; Alison D. Santucci , BA1,6xAlison D. SantucciSearch for articles by this author; Michael S. Rabin, MD1,2xMichael S. RabinSearch for articles by this author; Pasi A. Jänne , MD, PhD1,2xPasi A. JänneSearch for articles by this author; Shodeinde Coker , MD, MSc7xShodeinde CokerSearch for articles by this author; Jennifer R. Diamond , MD8xJennifer R. DiamondSearch for articles by this author; John Hilton , MD9xJohn HiltonSearch for articles by this author; Geoffrey I. Shapiro , MD, PhD2xGeoffrey I. ShapiroSearch for articles by this author; and Christopher A. French, MD3xChristopher A. FrenchSearch for articles by this author Show More 1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA2Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA3Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA4Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA5Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA6Boston Medical Center, Boston, MA7Bristol Myers Squibb, Lawrenceville, NJ8University of Colorado Cancer Center, Aurora, CO9Division of Medical Oncology, Ottawa Hospital, Ottawa, ON https://doi.org/10.1200/PO.22.00633 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologySUPPORTM.L.C. was supported by a Conquer Cancer Foundation‐ASCO Career Development Award. C.A.F. was supported by National Institutes of Health Grant No. R01 CA124633.AUTHOR CONTRIBUTIONSConception and design: Michael L. Cheng, Mizuki Nishino, Shodeinde Coker, Jennifer R. Diamond, Geoffrey I. Shapiro, Christopher A. FrenchAdministrative support: Pasi A Jänne, Geoffrey I. ShapiroProvision of study materials or patients: Michael L. Cheng, Michael S. Rabin, Jennifer R. Diamond, John Hilton, Geoffrey I. ShapiroCollection and assembly of data: Michael L. Cheng, Yeying Huang, Nhi Luong, Jaclyn LoPiccolo, Mizuki Nishino, Lynette M. Sholl, Lucian R. Chirieac, Alison D. Santucci, Michael S. Rabin, Shodeinde Coker, Jennifer R. Diamond, John Hilton, Geoffrey I. Shapiro, Christopher A. FrenchData analysis and interpretation: Michael L. Cheng, Yeying Huang, Jaclyn LoPiccolo, Lynette M. Sholl, Pasi A Jänne, Shodeinde Coker, Jennifer R. Diamond, John Hilton, Geoffrey I. Shapiro, Christopher A. FrenchManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Michael L. ChengHonoraria: Lynx Group, WebMD, Potomac Center for Medical EducationConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Mirati Therapeutics, Cepheid, Janssen, PfizerResearch Funding: Palleon Pharmaceuticals (Inst)Travel, Accommodations, Expenses: Daiichi Sankyo, AstraZeneca, GenzymeNhi LuongEmployment: NovartisMizuki NishinoConsulting or Advisory Role: AstraZenecaResearch Funding: AstraZeneca (Inst), Daiichi Sankyo (Inst), Canon Medical System (Inst)Lynette M. ShollStock and Other Ownership Interests: Moderna Therapeutics (I)Consulting or Advisory Role: Genentech (Inst), Lilly (Inst), AstraZenecaResearch Funding: Roche/Genentech (Inst), Bristol Myers Squibb (Inst)Alison D. SantucciEmployment: Boston Medical Center, Dana-Farber Cancer InstituteTravel, Accommodations, Expenses: Boston Medical Center, Dana-Farber Cancer InstituteMichael S. RabinStock and Other Ownership Interests: Acuity BioPasi A. JänneStock and Other Ownership Interests: Gatekeeper Pharmaceuticals, LoxoConsulting or Advisory Role: Pfizer, Boehringer Ingelheim, AstraZeneca, Merrimack, Chugai Pharma, Roche/Genentech, LOXO, Mirati Therapeutics, Araxes Pharma, Ignyta, Lilly, Takeda, Novartis, Biocartis, Voronoi Health Analytics, SFJ Pharmaceuticals Group, Sanofi, Biocartis, Daiichi Sankyo, Silicon Therapeutics, Nuvalent Inc, Eisai, Bayer, Syndax, AbbVie, Allorion Therapeutics, Accutar Biotech, Transcenta, Monte Rosa Therapeutics, Scorpion Therapeutics, Merus, Frontier Medicines, Hongyun Biotech, Duality BiologicsResearch Funding: AstraZeneca, Astellas Pharma, Daiichi Sankyo, Lilly, Boehringer Ingelheim, Puma Biotechnology, Takeda, Revolution MedicinesPatents, Royalties, Other Intellectual Property: I am a coinventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp. I receive postmarketing royalties from this inventionShodeinde CokerEmployment: Bristol Myers SquibbStock and Other Ownership Interests: Bristol Myers SquibbPatents, Royalties, Other Intellectual Property: Coinventor of novel conjugated interleukin 10, Co-inventor of BET inhibitor in combination with a JAK2 inhibitor for the treatment of myelofibrosisTravel, Accommodations, Expenses: Bristol Myers SquibbJennifer R. DiamondLeadership: OnKure (Inst)Stock and Other Ownership Interests: OnKureConsulting or Advisory Role: Gilead Sciences (Inst)Research Funding: Bristol Myers Squibb (Inst), Bayer (Inst), Merck (Inst), Deciphera (Inst), OnKure (Inst), Takeda (Inst), Cosmo Pharmaceuticals (Inst), Adlai Nortye (Inst), Gilead Sciences (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: OnKureJohn HiltonConsulting or Advisory Role: Merck, Lilly, Bristol Myers Squibb, Novartis, Pfizer, AstraZenecaResearch Funding: GlaxoSmithKline (Inst)Geoffrey I. ShapiroConsulting or Advisory Role: Lilly, Pfizer, Merck Serono, Cybrexa Therapeutics, Bayer, Fusion Pharmaceuticals, Bicycle Therapeutics, Artios, Boehringer Ingelheim, Concarlo, Atrin Pharmaceuticals, Syros Pharmaceuticals, Zentalis, CytomX Therapeutics, Blueprint Medicines, Kymera, Janssen Oncology, Xinthera, ImmunoMetResearch Funding: Pfizer (Inst), Bayer (Inst), Puma Biotechnology (Inst), Novartis (Inst), Cellceutix (Inst), Sanofi (Inst), Cyclacel (Inst), Mirati Therapeutics (Inst), AstraZeneca (Inst), GlaxoSmithKline (Inst), Lilly (Inst), Roche (Inst), CanBas (Inst), Merck Serono (Inst), Sierra Oncology (Inst), Syros Pharmaceuticals (Inst), Merck (Inst), Array BioPharma (Inst), Seagen (Inst), Clovis Oncology (Inst), Exelixis (Inst), Boehringer Ingelheim (Inst), Esperas Pharma (Inst), Amgen (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Tango Therapeutics (Inst), Bristol Myers Squibb/Medarex (Inst), Senhwa Biosciences (Inst), Biosplice (Inst), Cyteir (Inst), AbbVie (Inst)Patents, Royalties, Other Intellectual Property: Patent #: 9872874 Title: Dosage regimen for sapacitabine and seliciclib Issue Date: January 23, 2018, Provisional Patent #:62/538,319 Title: Compositions and methods for predicting response and resistance to CDK4/6 inhibition Filed: July 28, 2017Christopher A. FrenchResearch Funding: Epigenetix (Inst)No other potential conflicts of interest were reported.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".