Clinical Outcomes and Evolution of Clonal Hematopoiesis in Patients with Newly Diagnosed Multiple Myeloma

被引：9

作者：

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

Nzerem, Chidimma ^{[3
,5
]}

Redd, Robert ^{[6
]}

Dunford, Andrew ^{[3
]}

Leventhal, Matthew ^{[3
]}

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

Tahri, Sabrin ^{[1
,2
,3
,7
]}

El-Khoury, Habib ^{[1
,2
,3
]}

Steensma, David P. ^{[1
]}

Ebert, Benjamin L. ^{[1
,2
,3
]}

Soiffer, Robert J. ^{[1
]}

Keats, Jonathan J. ^{[8
]}

Mehr, Shaadi ^{[9
]}

Auclair, Daniel ^{[9
]}

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

Sperling, Adam S. ^{[1
,2
,3
,10
]}

Stewart, Chip ^{[3
]}

Getz, Gad ^{[2
,3
,11
,12
,13
]}

机构：

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

[2] Harvard Med Sch, Boston, MA USA

[3] Broad Inst MIT & Harvard, Cambridge, MA USA

[4] Icahn Sch Med Mt Sinai, Tish Canc Inst, Div Hematol & Med Oncol, New York, NY USA

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

[6] Dana Farber Canc Inst, Dept Data Sci, Boston, MA USA

[7] Erasmus MC, Dept Hematol, Canc Ctr, Rotterdam, Netherlands

[8] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ USA

[9] Multiple Myeloma Res Fdn, Norwalk, CT USA

[10] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA

[11] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[12] Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA

[13] Harvard & Broad Inst, Boston, MA 02142 USA

来源：

CANCER RESEARCH COMMUNICATIONS | 2023年 / 3卷 / 12期

关键词：

STEM-CELL TRANSPLANTATION; MONOCLONAL GAMMOPATHY; OPEN-LABEL; RISK; LENALIDOMIDE; MUTATIONS; THERAPY; DEXAMETHASONE; MAINTENANCE; BORTEZOMIB;

D O I：

10.1158/2767-9764.CRC-23-0093

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Clonal hematopoiesis (CH) at time of autologous stem cell transplant (ASCT) has been shown to be associated with decreased overall survival (OS) and progression-free survival (PFS) in patients with multiple myeloma not receiving immunomodulatory drugs (IMiD). However, the significance of CH in newly diagnosed patients, including transplant ineligible patients, and its effect on clonal evolution during multiple myeloma therapy in the era of novel agents, has not been well studied. Using our new algorithm to differentiate tumor and germline mutations from CH, we detected CH in approximately 10% of 986 patients with multiple myeloma from the Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) cohort (40/529 transplanted and 59/457 non-transplanted patients). CH was associated with increased age, risk of recurrent bacterial infections and cardiovascular disease. CH at time of multiple myeloma diagnosis was not associated with inferior OS or PFS regardless of undergoing ASCT, and all patients benefited from IMiD-based therapies, irrespective of the presence of CH. Serial sampling of 52 patients revealed the emergence of CH over a median of 3 years of treatment, increasing its prevalence to 25%, mostly with DNMT3A mutations.Significance: Using our algorithm to differentiate tumor and germline mutations from CH mutations, we detected CH in approximately 10% of patients with newly diagnosed myeloma, including both transplant eligible and ineligible patients. Receiving IMiDs improved outcomes irrespective of CH status, but the prevalence of CH significantly rose throughout myeloma-directed therapy.

引用

页码：2560 / 2571

页数：12

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