American Association for Cancer Research
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Supplementary Table from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma

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posted on 2023-04-01, 00:05 authored by Rosalinda Termini, David Žihala, Evangelos Terpos, Albert Perez-Montaña, Tomáš Jelínek, Marc Raab, Niels Weinhold, Elias K. Mai, Anna Luise Grab, Jill Corre, Francois Vergez, Antonio Sacco, Marco Chiarini, Viviana Giustini, Alessandra Tucci, Sara Rodriguez, Cristina Moreno, Cristina Perez, Catarina Maia, Esperanza Martín-Sánchez, Camilla Guerrero, Cirino Botta, Juan-Jose Garces, Aitziber Lopez, Luis-Esteban Tamariz-Amador, Felipe Prosper, Joan Bargay, Maria-Elena Cabezudo, Enrique M. Ocio, Roman Hájek, Joaquin Martinez-Lopez, Fernando Solano, Rebeca Iglesias, Artur Paiva, Catarina Geraldes, Helena Vitoria, Clara Gomez, Felipe De Arriba, Heinz Ludwig, Antoni Garcia-Guiñon, Maria Casanova, Adrian Alegre, Valentin Cabañas, Maialen Sirvent, Albert Oriol, Javier de la Rubia, José-Ángel Hernández-Rivas, Luis Palomera, Maria Sarasa, Pablo Rios, Noemi Puig, Maria-Victoria Mateos, Juan Flores-Montero, Alberto Orfao, Hartmut Goldschmidt, Hervé Avet-Loiseau, Aldo M. Roccaro, Jesus F. San-Miguel, Bruno Paiva
Supplementary Table from Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma


Centro de Investigación Biomédica en Red de Cáncer (CIBERONC)

Cancer Research UK (CRUK)



Black Swan Research Initiative of the International Myeloma Foundation

European Research Council (ERC)

CRIS Cancer Foundation

Riney Family Multiple Myeloma Research Program Fund

European Union

European Hematology Association (EHA)

Multiple Myeloma Research Foundation (MMRF)



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. 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. 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. 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.

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