Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma

被引：32

作者：

Termini, Rosalinda ^{[1
]}

Zihala, David ^{[2
,3
]}

Terpos, Evangelos ^{[4
]}

Perez-Montana, Albert ^{[5
]}

Jelinek, Tomas ^{[2
,3
]}

Raab, Marc ^{[6
,7
]}

Weinhold, Niels ^{[6
,7
]}

Mai, Elias K. ^{[6
,7
]}

Grab, Anna Luise ^{[6
,7
]}

Corre, Jill ^{[8
]}

Vergez, Francois ^{[8
]}

Sacco, Antonio ^{[9
]}

Chiarini, Marco ^{[9
]}

Giustini, Viviana ^{[9
]}

Tucci, Alessandra ^{[9
]}

Rodriguez, Sara ^{[1
]}

Moreno, Cristina ^{[1
]}

Perez, Cristina ^{[1
]}

Maia, Catarina ^{[1
]}

Martin-Sanchez, Esperanza ^{[1
]}

Guerrero, Camilla ^{[1
]}

Botta, Cirino ^{[10
]}

Garces, Juan-Jose ^{[1
]}

Lopez, Aitziber ^{[1
]}

Tamariz-Amador, Luis-Esteban

Prosper, Felipe ^{[1
]}

Bargay, Joan ^{[11
]}

Cabezudo, Maria-Elena ^{[12
]}

Ocio, Enrique M. ^{[13
]}

Hajek, Roman ^{[2
,3
]}

Martinez-Lopez, Joaquin ^{[14
]}

Solano, Fernando ^{[15
]}

Iglesias, Rebeca ^{[16
]}

Paiva, Artur ^{[17
]}

Geraldes, Catarina ^{[17
]}

Vitoria, Helena ^{[18
]}

Gomez, Clara ^{[19
]}

De Arriba, Felipe ^{[20
]}

Ludwig, Heinz ^{[21
]}

Garcia-Guinon, Antoni ^{[22
]}

Casanova, Maria ^{[23
]}

Alegre, Adrian ^{[24
]}

Cabanas, Valentin ^{[25
]}

Sirvent, Maialen ^{[26
]}

Oriol, Albert ^{[27
]}

de la Rubia, Javier ^{[28
]}

Hernandez-Rivas, Jose-Angel ^{[29
]}

Palomera, Luis ^{[30
]}

Sarasa, Maria ^{[31
]}

Rios, Pablo ^{[32
]}

机构：

[1] Clin Univ Navarra, Ctr Invest Med Aplicada CIMA, Inst Invest Sanitaria Navarra IDISNA, CIBER ONC CB16 12 00369 CB16 12 00489,CCUN, Pamplona, Spain

[2] Univ Hosp Ostrava, Dept Hematooncol, Ostrava, Czech Republic

[3] Univ Ostrava, Ostrava, Czech Republic

[4] Natl & Kapodistrian Univ Athens, Sch Med, Athens, Greece

[5] Hosp Univ Son Espases, Palma De Mallorca, Spain

[6] Heidelberg Univ, Dept Internal Med 5, Clin Hosp, Heidelberg, Germany

[7] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[8] INSERM, Unite 1037, Ctr Rech Cancerol Toulouse, Toulouse, France

[9] ASST Spedali Civili Brescia, Brescia, Italy

[10] Univ Palermo, Dept Hlth Promot Mother & Child Care Internal Med, Palermo, Italy

[11] Hosp Sont LLatzer, Palma De Mallorca, Spain

[12] Hosp St Joan Despi Moises Broggi ICO H, Barcelona, Spain

[13] Univ Cantabria, Hosp Univ Marques de Valdecilla IDIVAL, Santander, Spain

[14] Univ Complutense, Hosp Univ 12 Octubre, CNIO Madrid, Madrid, Spain

[15] Hosp Ntra Sra del Prado, Talavera De La Reina, Spain

[16] MD Anderson Canc Ctr, Madrid, Spain

[17] Ctr Hospitalare Univ Coimbra CHUC, Dept Clin Pathol, Flow Cytometry Unit UGOC, Coimbra, Portugal

[18] Ctr Hosp Univ Coimbra CHUC, Coimbra, Portugal

[19] Hosp Galdakao, Vizcaya, Spain

[20] Univ Murcia, Hosp Morales Meseguer, IMIB Arrixaca, Murcia, Spain

[21] Clin Ottakring, Wilhelminen Canc Res Inst, Vienna, Austria

[22] Hosp Arnau Vilanova, Lleida, Spain

[23] Hosp Costa Sol Marbella, Marbella, Spain

[24] Hosp Princesa, Madrid, Spain

[25] Univ Murcia, Hosp Virgen de la Arrixaca Murcia, IMIB Arrixaca, Murcia, Spain

[26] Hosp Univ Donostia, San Sebastian, Spain

[27] Inst Catala Oncol, Inst Josep Carreras, Badalona, Spain

[28] Catholic Univ Valencia, Univ Hosp La Fe, Sch Med & Dent, CIBERONC CB16 12 00284, Valencia, Spain

[29] Univ Complutense, Hosp Univ Infanta Leonor, Dept Med, Madrid, Spain

[30] Hosp Clin Univ Lozano Blesa, Zaragoza, Spain

[31] Hosp Laredo, Laredo, Spain

[32] Hosp Nuestra Senora de la Candelara, Santa Cruz De Tenerife, Spain

[33] Univ Salamanca, Hosp Univ Salamanca, Inst Invest Biomed Salamanca IBSAL, Salamanca, Spain

[34] Univ Salamanca, Translat & Clin Res Program, Ctr Invest Canc IBMCC USAL, CSIC,Dept Med,Cytometry Serv,Inst Invest Biosanit, Salamanca, Spain

[35] Univ Salamanca, CIBER ONC 0316 12 00400, Salamanca, Spain

来源：

CLINICAL CANCER RESEARCH | 2022年 / 28卷 / 21期

基金：

欧洲研究理事会;

关键词：

MONOCLONAL GAMMOPATHY; PLASMA-CELLS; PROGRESSION; QUANTIFICATION; CRITERIA;

D O I：

10.1158/1078-0432.CCR-22-1594

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under-and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model.Experimental Design: We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment.Results: Patients with >0.015% versus <= 0.015% CTCs at baseline had a median time-to-progression of 17 months versus not reached (HR, 4.9; P < 0.001). Presence of>20% BM PCs had no prognostic value in a multivariate analysis that included serum free light-chain ratio >20, >2 g/dL M-protein, and >0.015% CTCs. The 20/2/20 and 20/2/0.015 models yielded similar risk stratification (C-index of 0.76 and 0.78). The combination of the 20/2/0.015 model with an immune risk score based on the percentages of SLAN+ and SLAN- nonclassical monocytes, CD69+HLADR+ cytotoxic NK cells, and CD4+CXCR3+ stem central memory T cells, allowed patient' stratification into low, intermediate-low, intermediate-high, and high-risk disease with 0%, 20%, 39%, and 73% rates of progression at 2 years.Conclusions: This study showed that CTCs outperform BM PCs for assessing tumor burden. Additional analysis in larger series are needed to define a consensus cutoff of CTCs for minimally invasive stratification of SMM.

引用

页码：4771 / 4781

页数：11

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