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Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma

Autores: Tamariz Amador, Luis Esteban (Autor de correspondencia); Rodríguez Otero, Paula (Autor de correspondencia); Jiménez-Ubieto, A.; Rosiñol, L.; Oriol, A.; Ríos, R.; Sureda, A.; Blanchard, M. J.; Hernández, M. T.; Cabañas Perianes, V.; Jarque, I.; Bargay, J.; Gironella, M.; De Arriba, F.; Palomera, L.; González-Montes, Y.; Martí, J. M.; Krsnik, I.; Arguiñano, J. M.; González, M. E.; Casado, L. F.; González-Rodríguez, A. P.; López-Anglada, L.; Puig, N.; Cedena, M. T.; Paiva, Bruno; Mateos, M. V.; San Miguel Izquierdo, Jesús; Lahuerta, J. J.; Bladé, J.; Fernández de Trocóniz Fernández, José Ignacio
ISSN: 2152-2669
Volumen: 22
Número: 9
Páginas: e844 - e852
Fecha de publicación: 2022
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.