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- Title
Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma.
- Authors
Tamariz-Amador, Luis-Esteban; Rodríguez-Otero, Paula; Jiménez-Ubieto, Ana; Rosiñol, Laura; Oriol, Albert; Ríos, Rafael; Sureda, Anna; Blanchard, Maria Jesus; Hernández, Miguel Teodoro; Perianes, Valentin Cabañas; Jarque, Isidro; Bargay, Juan; Gironella, Mercedes; Arriba, Felipe De; Palomera, Luis; Gonzalez-Montes, Yolanda; Martí, Josep M.; Krsnik, Isabel; Arguiñano, José María; González, María Esther
- Abstract
Response kinetics is not well-established as a prognostic marker in multiple myeloma (MM). We developed a mathematical model to assess the prognostic value of serum monoclonal component (MC) response kinetics during 6 induction cycles in 373 newly diagnosed MM patients. The model calculated a "resistance" parameter that reflects the stagnation in the response after an initial descent, dividing the patients into two kinetics categories with significantly different progression-free survival (PFS). 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 0.440.93; 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.
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2022, Vol 22, Issue 9, pe844
- ISSN
2152-2650
- Publication type
Article
- DOI
10.1016/j.clml.2022.04.024