Publicaciones científicas

Circulating tumor and immune cells for minimally invasive risk stratification of smoldering multiple myeloma

01-nov-2022 | Revista: Clinical Cancer Research

Rosalinda Termini  1 , David Zihala  2 , Evangelos Terpos  3 , Albert Pérez-Montaña  4 , Tomas Jelinek  5 , Marc Raab  6 , Niels Weinhold  7 , Elias K Mai  7 , Anna Luise Grab  7 , Jill Corre  8 , Francois Vergez  9 , Antonio Sacco  10 , Marco Chiarini  10 , Viviana Giustini  10 , Alessandra Tucci  11 , Sara Rodríguez  12 , Cristina Moreno  13 , Cristina Perez  14 , Catarina Maia  15 , Esperanza Martin-Sanchez  16 , Camila Guerrero  17 , Cirino Botta  18 , Juan-Jose Garcés  19 , Aitziber Lopez  14 , Luis-Esteban Tamariz-Amador  1 , Felipe Prósper  20 , Joan Bargay  21 , Maria-Elena Cabezudo  22 , Enrique M Ocio  23 , Roman Hájek  24 , Joaquin Martinez-Lopez  25 , Fernando Solano  26 , Rebeca Iglesias  27 , Artur Paiva  28 , Catarina Geraldes  29 , Helena Matos Silva  30 , Clara Gomez  31 , Felipe De Arriba  32 , Heinz Ludwig  33 , Antoni Garcia-Guiñon  34 , Maria Casanova  35 , Adrian Alegre  36 , Valentin Cabañas  37 , Maialen Sirvent  38 , Albert Oriol  39 , Javier De la Rubia  40 , José-Ángel Hernández-Rivas  41 , Luis Palomera  42 , Maria Sarasa  43 , Pablo Rios  44 , Noemi Puig  45 , Maria-Victoria Mateos  46 , Juan Flores-Montero  47 , Alberto Orfao  48 , Hartmut Goldschmidt  49 , Herve Avet-Loiseau  50 , Aldo M Roccaro  10 , Jesus F San-Miguel  51 , Bruno Paiva  52


Purpose: Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under and over-treatment. We hypothesized that replacing bone marrow (BM) plasma cells (PCs) for circulating tumor cells (CTCs), 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 SMM patients 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 three years since enrollment.

Results: Patients with >0.015% vs ≤0.015% CTCs at baseline had a median time-to-progression of 17 months vs not reached (hazard ratio: 4.9, P<.001). Presence of >20% BM PCs had no prognostic value in a multivariate analysis that included serum free light-chain ratio >20, >2g/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- non-classical 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 two 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.

CITA DEL ARTÍCULO Clin Cancer Res. 2022 Nov 1;28(21):4771-4781. doi: 10.1158/1078-0432.CCR-22-1594.