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

2022; American Association for Cancer Research; Volume: 28; Issue: 21 Linguagem: Inglês

10.1158/1078-0432.ccr-22-1594

1557-3265

Rosalinda Termini, David Žihala, Evangelos Terpos, Albert Pérez-Montaña, Tomáš Jelı́nek, Marc S. Raab, Niels Weinhold, K. Elias, Anna Luise Grab, Jill Corre, François Vergez, Antonio Sacco, Marco Chiarini, Viviana Giustini, Alessandra Tucci, Sara Rodríguez, Cristina Moreno, Cristina Pérez, Catarina Maia, Esperanza Martín‐Sánchez, Camilla Guerrero, Cirino Botta, Juan‐José Garcés, Aitziber López, Luis‐Esteban Tamariz‐Amador, Felipe Prósper, Joan Bargay, Maria-Elena Cabezudo, Enrique M. Ocio, Roman Hájek, Joaquín Martínez‐López, Fernando Solano, Rebeca Iglesias, Artur Paiva, Catarina Geraldes, Helena Vitória, Clara Gómez, Felipe de Arriba, Heinz Ludwig, Antoni García‐Guiñón, María Casanova, Adrián Alegre, Valentín Cabañas, Maialen Sirvent, Albert Oriol, Javier de la Rubia, José‐Ángel Hernández‐Rivas, Luis Palomera, Maria Sarasa, Pablo Rios, Noemí Puig, María‐Victoria Mateos, Juan Flores‐Montero, Alberto Órfão, Hartmut Goldschmidt, Hervé Avet‐Loiseau, Aldo M. Roccaro, Jesús F. San Miguel, Bruno Paiva,

Chemokine receptors and signaling

Abstract 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.