Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma
Keywords: 
Área de Medicina Clínica y Epidemiología
Early treatment failure
Newly diagnosed myeloma
Time to best response
Prognostic marker
Depht of response
Issue Date: 
2022
ISSN: 
2152-2669
Note: 
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Citation: 
Tamariz-Amador, L. (Luis Esteban); Rodríguez-Otero, P. (Paula); Jiménez-Ubieto, A.; et al. "Prognostic value of serum paraprotein response kinetics in patients with newly diagnosed multiple myeloma". Clinical Lymphoma Myeloma And Leukemia. 22 (9), 2022, e844 - e852
Abstract
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.

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