Lahuerta-Vargas, J.J. (Juan José)
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- Nota previa(T6 Ediciones, 2002-03-14) Lahuerta-Vargas, J.J. (Juan José)
- Molecular profiling of immunoglobulin heavychain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients(2020) Gonzalez-Calle, V. (Veronica); Martínez-López, J. (Joaquín); Garcia-Alvarez, M. (María); Gonzalez, M. (Marcos); Gironella, M. (Mercedes); Bladé, J. (Joan); Prieto-Conde, M.I. (María Isabel); Sarasquete, M.E. (María E.); García-Sanz, R. (Ramón); Alcoceba, M. (Miguel); Medina, A. (Alejandro); Mateos, M.V. (María Victoria); Hernandez, M.T. (Miguel Teodoro); Balanzategui, A. (Ana); Puig, N. (Noemí); Barrio, S. (Santiago); Pérez-Cuenca, I. (Isabel); Lahuerta-Vargas, J.J. (Juan José); Gutierrez, N.C. (Norma C.); Escalante, L.F. (Luis Fernando); Oriol, A. (Albert); Sureda-Balari, A. M. (Anna Maria); Chillón, M.C. (María del Carmen); Calasanz-Abinzano, M.J. (Maria Jose); San-Miguel, J.F. (Jesús F.); Jiménez, C. (Cristina)Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavychain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.
- Las acciones térmicas en las cubiertas planas(Servicio de Publicaciones de la Universidad de Navarra, 1990) Lahuerta-Vargas, J.J. (Juan José); Gutiérrez-Fernández, M.Á. (Miguel Ángel)
- Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma(ASCO Publications, 2022) Garcés-Latre, J.J. (Juan José); Cedena, M.T. (María Teresa); Puig, N. (Noemí); Burgos, L. (Leire); Pérez, J.J. (José J.); Cordón, L. (Lourdes); Flores-Montero, J. (Juan); Sanoja-Flores, L. (L.); Calasanz-Abinzano, M.J. (Maria Jose); Ortiol, A. (Albert); Blanchard, M.J. (María Jesús); Ríos, R. (Rafael) de los; Martin, J. (Jesus); Martínez-Martínez, R. (Rafael); Bargay, J. (Joan); Sureda-Balari, A. (Anna); Rubia, J. (Javier) de la; Hernandez, M.T. (Miguel Teodoro); Rodriguez-Otero, P. (Paula); de-la-Cruz, J. (Javier); Orfao, A. (Alberto); Mateos, M.V. (María Victoria); Martínez-López, J. (Joaquín); Lahuerta-Vargas, J.J. (Juan José); Rosiñol, L. (Laura); Bladé, J. (Joan); San-Miguel, J.F. (Jesús F.); Paiva, B. (Bruno)Purpose Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined. Patients and Methods CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment. Results CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS. Conclusion Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.
- Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma(ASH Publications, 2024) Guerrero, C. (Camila); Puig, N. (Noemí); Cedena, M.T. (María Teresa); Calasanz-Abinzano, M.J. (Maria Jose); Gutierrez, N.C. (Norma C.); Fernández, M. (Manuela); Oriol, A. (Albert); Ríos-Tamayo, R. (Rafael); Hernandez, M.T. (Miguel Teodoro); Martinez-Monge, R. (Rafael); Bargay, J. (Joan); Arriba, F. (Felipe) de; Palomera, L. (Luis); González-Rodriguez, A.P. (Ana Pilar); González, M.S. (Marta Sonia); Orfao, A. (Alberto); Mateos, M.V. (María Victoria); Martínez-López, J. (Joaquín); Rosiñol, L. (Laura); Bladé, J. (Joan); Lahuerta-Vargas, J.J. (Juan José); San-Miguel, J.F. (Jesús F.); Pavia, B. (Bruno)The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible patients with multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreating them. Here, we studied 267 newly diagnosed transplant-eligible patients with MM enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having 0 vs 1 vs ≥2 risk factors (ISS 3, ≥0.01% CTCs, and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33%, and 57%, respectively (P < .001). Thus, these easily measurable risk factors could help refine the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. This trial was registered at www.clinicaltrials.gov as NCT01916252 and NCT02406144.