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Title: | Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma |
Author: | Tamariz Amador, Luis Esteban Rodríguez Otero, Paula Jiménez Ubieto, Ana Rosiñol, Laura Oriol, Albert Ríos, Rafael Sureda, Anna Blanchard, Maria Jesus Hernández, Miguel Teodoro Cabañas Perianes, Valentin Jarque, Isidro Bargay, Juan Gironella, Mercedes De Arriba, Felipe Palomera, Luis Gonzalez Montes, Yolanda Martí, Josep M. Krsnik, Isabel Arguiñano, José María González, María Esther Casado, Luis Felipe González Rodriguez, Ana Pilar López Anglada, Lucía Puig, Noemi Cedena, Maria Teresa Paiva, Bruno Mateos, María Victoria San Miguel, Jesús Lahuerta, Juan José Bladé, J. (Joan) Trocóniz, Iñaki F. |
Keywords: | Mieloma múltiple Pronòstic mèdic Multiple myeloma Prognosis |
Issue Date: | 1-Sep-2022 |
Publisher: | Elsevier BV |
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 0.44-0.93; 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. (C) 2022 The Authors. Published by Elsevier Inc. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.clml.2022.04.024 |
It is part of: | Clinical Lymphoma Myeloma and Leukemia, 2022, vol. 22, issue. 9, p. e844-e852 |
URI: | http://hdl.handle.net/2445/190749 |
Related resource: | https://doi.org/10.1016/j.clml.2022.04.024 |
ISSN: | 2152-2669 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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