Casado, L.F. (Luis Felipe)
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- Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma(2022) Blanchard, M.J. (María Jesús); González, M.E. (María Esther); Cedena, M.T. (María Teresa); Casado, L.F. (Luis Felipe); Krsnik, I. (Isabel); Ríos, R. (Rafael) de los; Gironella, M. (Mercedes); Bladé, J. (Joan); Mateos, M.V. (María Victoria); Arriba, F. (Felipe) de; Troconiz, I.F. (Iñaki F.); Hernandez, M.T. (Miguel Teodoro); Rosiñol, L. (Laura); Puig, N. (Noemí); Lopez-Anglada, L. (Lucia); Arguiñano, J.M. (José María); Palomera, L. (Luis); Lahuerta, J.J. (Juan José); Rodriguez-Otero, P. (Paula); Paiva, B. (Bruno); Jarque, I. (Isidro); Oriol, A. (Albert); Marti, J.M. (J.M.); Sureda-Balari, A. M. (Anna Maria); González-Rodriguez, A.P. (Ana Pilar); Bargay, J. (Joan); Gonzalez-Montes, Y. (Yolanda); Jiménez-Ubieto, A. (Ana); San-Miguel, J.F. (Jesús F.); Tamariz-Amador, L.E. (Luis Esteban); Cabañas, V. (Valentín)Introduction Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). Materials and Methods We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a “resistance” parameter that reflects the stagnation in the response after an initial descent. Results Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. Conclusion This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.
- Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma(2022) Blanchard, M.J. (María Jesús); González, M.E. (María Esther); Cedena, M.T. (María Teresa); Casado, L.F. (Luis Felipe); Krsnik, I. (Isabel); Ríos, R. (Rafael) de los; Gironella, M. (Mercedes); Bladé, J. (Joan); Mateos, M.V. (María Victoria); Arriba, F. (Felipe) de; Troconiz, I.F. (Iñaki F.); Hernandez, M.T. (Miguel Teodoro); Rosiñol, L. (Laura); Puig, N. (Noemí); Lopez-Anglada, L. (Lucia); Arguiñano, J.M. (José María); Palomera, L. (Luis); Lahuerta, J.J. (Juan José); Rodriguez-Otero, P. (Paula); Paiva, B. (Bruno); Jarque, I. (Isidro); Oriol, A. (Albert); Marti, J.M. (J.M.); Sureda-Balari, A. M. (Anna Maria); González-Rodriguez, A.P. (Ana Pilar); Bargay, J. (Joan); Gonzalez-Montes, Y. (Yolanda); Jiménez-Ubieto, A. (Ana); San-Miguel, J.F. (Jesús F.); Tamariz-Amador, L.E. (Luis Esteban); Cabañas, V. (Valentín)Introduction: Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). Materials and Methods: We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a ¿resistance¿ parameter that reflects the stagnation in the response after an initial descent. Results: Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P =.02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P =.02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P <.002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. Conclusion: This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies.
- Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality(2020) Blanchard, M.J. (María Jesús); Casado, L.F. (Luis Felipe); Prieto, E. (Elena); Martínez-López, J. (Joaquín); Krsnik, I. (Isabel); Gironella, M. (Mercedes); Bladé, J. (Joan); Lopez-de-la-Guía, A. (Ana); Mateos, J.J. (Juan José); Mateos, M.V. (María Victoria); Encinas, C. (Cristina); Hernández-Rivas, J.Á. (José Ángel); Senin, M.A. (María Alicia); Escalante, F. (Fernando); Fernández-de-Larrea, C. (Carlos); de-la-Cruz, J. (Javier); Giménez, E. (Eugenio); Lahuerta, J.J. (Juan José); Caminos, N. (Nerea); de-la-Puerta, J.E. (José Enrique); Conde, D. (Diego); Sureda-Balari, A. M. (Anna Maria); Riaza-Grau, R. (Rosalía); Martínez-Barranco, P. (Pilar); San-Miguel, J.F. (Jesús F.)There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate–severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.