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

被引：31

作者：

Sklavenitis-Pistofidis, Romanos ^{[1
,2
,3
,4
]}

Aranha, Michelle P. ^{[1
,2
,4
]}

Redd, Robert A. ^{[5
]}

Baginska, Joanna ^{[1
]}

Haradhvala, Nicholas J. ^{[4
,6
]}

Hallisey, Margaret ^{[1
]}

Dutta, Ankit K. ^{[1
,2
,3
,4
]}

Savell, Alexandra ^{[1
,3
]}

Varmeh, Shohreh ^{[1
,3
,4
]}

Heilpern-Mallory, Daniel ^{[1
,4
]}

Ujwary, Sylvia ^{[1
,2
,3
,4
]}

Zavidij, Oksana ^{[1
,2
,3
,4
]}

Aguet, Francois ^{[4
]}

Su, Nang K. ^{[1
,2
,3
,4
]}

Lightbody, Elizabeth D. ^{[1
,2
,3
,4
]}

Bustoros, Mark ^{[1
,2
,3
,4
]}

Tahnri, Sabrin ^{[1
,2
,3
,4
]}

Mouhieddine, Tarek H. ^{[1
,2
,3
,4
]}

Wu, Ting ^{[4
]}

Flechon, Lea ^{[7
]}

Anand, Shankara ^{[4
]}

Rosenblatt, Jacalyn M. ^{[8
]}

Zonder, Jeffrey ^{[9
]}

Vredenburgh, James J. ^{[10
]}

Boruchov, Adam ^{[10
]}

Bhutani, Manisha ^{[11
]}

Usmani, Saad Z. ^{[11
]}

Matous, Jeffrey ^{[12
]}

Yee, Andrew J. ^{[13
]}

Jakubowiak, Andrzej ^{[14
]}

Laubach, Jacob ^{[1
]}

Manier, Salomon ^{[7
,15
]}

Nadeem, Omar ^{[1
,3
]}

Richardson, Paul ^{[1
,2
]}

Badros, Ashraf Z. ^{[16
]}

Mateos, Maria-Victoria ^{[17
]}

Trippa, Lorenzo ^{[5
]}

Getz, Gad ^{[2
,4
,13
,18
]}

Ghobrial, Irene M. ^{[1
,2
,3
,4
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Harvard Med Sch, Dana Farber Canc Inst, Ctr Prevent Progress CPOP, Med Oncol, Boston, MA 02215 USA

[4] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[5] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[6] Harvard Univ, Harvard Grad Program Biophys, Cambridge, MA 02138 USA

[7] Lille Univ, INSERM UMRS1277, CNRS UMR9020, F-59000 Lille, France

[8] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[9] Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA

[10] St Francis Hosp & Med Ctr, Canc Ctr, Hartford, CT 06105 USA

[11] Levine Canc Inst, Charlotte, NC 28204 USA

[12] Colorado Blood Canc Inst, Denver, CO 80218 USA

[13] Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA

[14] Univ Chicago Canc Ctr, Chicago, IL 60637 USA

[15] Lille Univ, CHU Lille, Dept Hematol, F-59000 Lille, France

[16] Univ Maryland Marlene, Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA

[17] Univ Hosp Salamanca, Inst Invest Biomed Salamanca, Salamanca 37007, Spain

[18] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

来源：

CANCER CELL | 2022年 / 40卷 / 11期

基金：

美国国家卫生研究院;

关键词：

MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; BONE-MARROW; MUTATIONS; DEXAMETHASONE; CRITERIA;

D O I：

10.1016/j.ccell.2022.10.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 charac-terization 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)+ CD8+ effector memory T (TEM) cells may be associated with treatment response. Last, we uncover similarities between immune alterations observed in the BM and PB, suggesting that PB-based immune profiling may have diagnostic and prognostic utility.

引用

页码：1358 / +

页数：25

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