Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma.

Humans Biomarkers Disease Progression Immunologic Factors Immunotherapy Lenalidomide / adverse effects Multiple Myeloma / drug therapy Smoldering Multiple Myeloma / therapy Clinical Trials, Phase II as Topic
bone marrow granzyme K immune biomarkers immune profiling immunotherapy peripheral blood single-cell RNA sequencing single-cell TCR sequencing smoldering multiple myeloma

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
14 11 2022
Historique:
received: 26 06 2021
revised: 03 08 2022
accepted: 18 10 2022
entrez: 15 11 2022
pubmed: 16 11 2022
medline: 19 11 2022
Statut: ppublish

Résumé

Patients with smoldering multiple myeloma (SMM) are observed until progression, but early treatment may improve outcomes. We conducted a phase II trial of elotuzumab, lenalidomide, and dexamethasone (EloLenDex) in patients with high-risk SMM and performed single-cell RNA and T cell receptor (TCR) sequencing on 149 bone marrow (BM) and peripheral blood (PB) samples from patients and healthy donors (HDs). We find that early treatment with EloLenDex is safe and effective and provide a comprehensive characterization of alterations in immune cell composition and TCR repertoire diversity in patients. We show that the similarity of a patient's immune cell composition to that of HDs may have prognostic relevance at diagnosis and after treatment and that the abundance of granzyme K (GZMK)

Identifiants

DOI: 10.1016/j.ccell.2022.10.017 PMID: 36379208 PMC: PMC10019228
pubmed: 36379208
pii: S1535-6108(22)00508-6
doi: 10.1016/j.ccell.2022.10.017
pmc: PMC10019228
mid: NIHMS1849232
pii:
doi:

Substances chimiques

Biomarkers 0
Immunologic Factors 0
Lenalidomide F0P408N6V4

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1358-1373.e8

Subventions

Organisme : NCI NIH HHS
ID : R01 CA205954
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests N.J.H. is a consultant for Constellation Pharmaceuticals. F.A. is an employee of Illumina Inc. O.Z. is an employee of Ikena Oncology and a stockholder in Ikena Oncology and Morphosys AG. G.G. receives research funds from IBM and Pharmacyclics and is an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, POLYSOLVER, SignatureAnalyzer-GPU, and MSIDetect. He is also a founder and consultant of and holds privately held equity in Scorpion Therapeutics. I.M.G. has a consulting or advisory role with AbbVie, Adaptive, Amgen, Aptitude Health, Bristol Myers Squibb, GlaxoSmithKline, Huron Consulting, Janssen, Menarini Silicon Biosystems, Oncopeptides, Pfizer, Sanofi, Sognef, Takeda, The Binding Site, and Window Therapeutics and has received speaker fees from Vor Biopharma and Veeva Systems, Inc., and her spouse is the CMO and equity holder of Disc Medicine. S.M. has a consulting role with Abbvie, Adaptive Biotechnology, Amgen, Celgene/BMS, GlaxoSmithKline, Janssen, Novartis, Oncopeptides, Regeneron, Roche, and Takeda and has received research funding from Abbvie, Adaptive Biotechnology, Amgen, Celgene/BMS, GlaxoSmithKline, Janssen, Novartis, Oncopeptides, Regeneron, Roche, and Takeda. A.J.Y. has a consulting role with Adaptive Biotechnologies, Amgen, BMS, Celgene, GSK, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda and has received research funding from Amgen, Janssen, and Takeda. M.B. is a consultant for Sanofi, Genzyme, and Janssen and has received research funding from MedImmune, Janssen, Legend Biotech, Amgen, Celularity, Bristol Myers Squibb, Celgene, Bluebird bio, Millennium, Takeda, Cerecor (currently Avalo Therapeutics), and C4 Therapeutics. M.B has an advisory role and received honoraria from Bristol Myers Squibb, Takeda, Janssen, and Menarini. T.H.M. received advisory board fees from Legend Biotech. R.S.-P., G.G., and I.M.G. are co-inventors on a patent application related to this work (PCT/US22/74839).

Références

J Clin Oncol. 2020 Jul 20;38(21):2380-2389
pubmed: 32442065
N Engl J Med. 2007 Jun 21;356(25):2582-90
pubmed: 17582068
Nat Cancer. 2020 May;1(5):493-506
pubmed: 33409501
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Leukemia. 2020 Jan;34(1):322-326
pubmed: 31439946
JCI Insight. 2019 Apr 23;5:
pubmed: 31013254
Nucleic Acids Res. 2013 Apr 1;41(6):e67
pubmed: 23303777
Cell Syst. 2019 Apr 24;8(4):281-291.e9
pubmed: 30954476
Nat Methods. 2018 Jul;15(7):531-534
pubmed: 29941871
Nat Commun. 2018 Aug 22;9(1):3363
pubmed: 30135448
Nat Commun. 2015 Dec 07;6:8866
pubmed: 26638776
Cancers (Basel). 2020 May 13;12(5):
pubmed: 32414145
Cell. 2013 Feb 14;152(4):714-26
pubmed: 23415222
Blood. 2015 May 14;125(20):3069-75
pubmed: 25838344
BMC Med Res Methodol. 2012 Feb 01;12:9
pubmed: 22297116
Eur J Cancer. 2022 Oct;174:243-250
pubmed: 36067617
Nat Biotechnol. 2012 May;30(5):413-21
pubmed: 22544022
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Nat Commun. 2021 Jan 12;12(1):293
pubmed: 33436579
Genome Biol. 2014;15(12):550
pubmed: 25516281
Lancet Oncol. 2014 Nov;15(12):e538-48
pubmed: 25439696
Blood. 2009 May 28;113(22):5418-22
pubmed: 19234139
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
J Exp Med. 2003 Dec 1;198(11):1753-7
pubmed: 14638846
Nature. 2014 Jan 23;505(7484):495-501
pubmed: 24390350
Bioinformatics. 2020 Feb 15;36(4):1150-1158
pubmed: 31501871
Gigascience. 2020 Dec 26;9(12):
pubmed: 33367645
Nat Immunol. 2020 Dec;21(12):1552-1562
pubmed: 33046887
STAR Protoc. 2022 Feb 17;3(1):101163
pubmed: 35243367
Nat Commun. 2021 Mar 25;12(1):1861
pubmed: 33767199
J Clin Oncol. 2020 Apr 10;38(11):1126-1137
pubmed: 31652094
Am Soc Clin Oncol Educ Book. 2015;:e484-92
pubmed: 25993213
Nat Genet. 2016 Jun;48(6):600-606
pubmed: 27111033
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):673-681
pubmed: 34889380
Bioinformatics. 2011 Sep 15;27(18):2601-2
pubmed: 21803805
F1000Res. 2016 Aug 31;5:2122
pubmed: 27909575
Blood. 2016 Mar 3;127(9):1151-62
pubmed: 26668134
Hum Mutat. 2015 Apr;36(4):E2423-9
pubmed: 25703262
Blood Cancer J. 2020 Oct 16;10(10):102
pubmed: 33067414
Nat Med. 2016 Nov;22(11):1351-1357
pubmed: 27723723
Blood. 2007 Oct 1;110(7):2586-92
pubmed: 17576818
F1000Res. 2021 Sep 28;10:979
pubmed: 35814628
N Engl J Med. 2013 Aug 1;369(5):438-47
pubmed: 23902483
Bioinformatics. 2012 Jul 15;28(14):1811-7
pubmed: 22581179
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601

Auteurs

Romanos Sklavenitis-Pistofidis (R)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Michelle P Aranha (MP)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Robert A Redd (RA)

Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Joanna Baginska (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Nicholas J Haradhvala (NJ)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.

Margaret Hallisey (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Ankit K Dutta (AK)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Alexandra Savell (A)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

Shohreh Varmeh (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Daniel Heilpern-Mallory (D)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Sylvia Ujwary (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Oksana Zavidij (O)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Francois Aguet (F)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Nang K Su (NK)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Elizabeth D Lightbody (ED)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Mark Bustoros (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Sabrin Tahri (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Tarek H Mouhieddine (TH)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Ting Wu (T)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Lea Flechon (L)

INSERM UMRS1277, CNRS UMR9020, Lille University, 59000 Lille, France.

Shankara Anand (S)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Jacalyn M Rosenblatt (JM)

Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Jeffrey Zonder (J)

Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.

James J Vredenburgh (JJ)

St. Francis Hospital and Cancer Center, Hartford, CT 06105, USA.

Adam Boruchov (A)

St. Francis Hospital and Cancer Center, Hartford, CT 06105, USA.

Manisha Bhutani (M)

Levine Cancer Institute, Charlotte, NC 28204, USA.

Saad Z Usmani (SZ)

Levine Cancer Institute, Charlotte, NC 28204, USA.

Jeffrey Matous (J)

Colorado Blood Cancer Institute, Denver, CO 80218, USA.

Andrew J Yee (AJ)

Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.

Andrzej Jakubowiak (A)

University of Chicago Cancer Center, Chicago, IL 60637, USA.

Jacob Laubach (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Salomon Manier (S)

INSERM UMRS1277, CNRS UMR9020, Lille University, 59000 Lille, France; Department of Hematology, CHU Lille, Lille University, 59000 Lille, France.

Omar Nadeem (O)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

Paul Richardson (P)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

Ashraf Z Badros (AZ)

University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA.

Maria-Victoria Mateos (MV)

University Hospital of Salamanca - Instituto de Investigación Biomédica de Salamanca, 37007 Salamanca, Spain.

Lorenzo Trippa (L)

Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Gad Getz (G)

Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: gadgetz@broadinstitute.org.

Irene M Ghobrial (IM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Prevention of Progression (CPOP), Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: irene_ghobrial@dfci.harvard.edu.

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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Isoindoles › Phtalimides › Lénalidomide › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Paraprotéinémies › Myélome multiple › Immune biomarkers of response to immunotherapy...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Paraprotéinémies › Myélome multiple indolent › Immune biomarkers of response to immunotherapy...
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