Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
Por:
Tamariz-Amador, LE, Rodriguez-Otero, P, Jimenez-Ubieto, A, Rosinol, L, Oriol, A, Rios, R, Sureda, A, Blanchard, MJ, Hernandez, MT, Perianes, VC, Jarque, I, Bargay, J, Gironella, M, De Arriba, F, Palomera, L, Gonzalez-Montes, Y, Marti, JM, Krsnik, I, Arguinano, JM, Gonzalez, ME, Casado, LF, Gonzalez-Rodriguez, AP, Lopez-Anglada, L, Puig, N, Cedena, MT, Paiva, B, Mateos, MV, San-Miguel, J, Lahuerta, JJ, Blade, J and Troconiz, IF
Publicada:
1 sep 2022
Ahead of Print:
1 ago 2022
Resumen:
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.
Filiaciones:
Tamariz-Amador, LE:
Clin Univ Navarra, Ctr Invest Med Aplicada CIMA, CIBERONC, IDISNA,CCUN, Pamplona, Spain
Rodriguez-Otero, P:
Clin Univ Navarra, Ctr Invest Med Aplicada CIMA, CIBERONC, IDISNA,CCUN, Pamplona, Spain
Jimenez-Ubieto, A:
Hosp 12 Octubre, Madrid, Spain
Rosinol, L:
Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain
:
Inst Catala Oncol, Badalona, Spain
Inst Josep Carreras, Badalona, Spain
Rios, R:
Hosp Univ Puerta Hierro, Madrid, Spain
Sureda, A:
Univ Barcelona, Inst Catala Oncol, IDIBELL, Hosp Duran & Reynals, Barcelona, Spain
Blanchard, MJ:
Hosp Ramon & Cajal, Madrid, Spain
Hernandez, MT:
Hosp Univ Canarias, Santa Cruz De Tenerife, Spain
Perianes, VC:
Hosp Virgen La Arrixaca, Murcial, Spain
Jarque, I:
Hosp La Fe, Valencia, Spain
Bargay, J:
Hosp Son Llatzer, Palma De Mallorca, Spain
Gironella, M:
Hosp Valle De Hebron, Barcelona, Spain
De Arriba, F:
Univ Murcia, Hosp Univ Morales Meseguer, IMIB Arrixaca, Murcia, Spain
Palomera, L:
Hosp Clin Lozano Blesa, Zaragoza, Spain
Gonzalez-Montes, Y:
Hosp Josep Trueta, Girona, Spain
Marti, JM:
Hosp Mutua Terrassa, Terrassa, Spain
Krsnik, I:
Hosp Puerta Hierro, Madrid, Spain
Arguinano, JM:
Hosp Univ Navarra, Pamplona, Spain
Gonzalez, ME:
Hosp Cabuenes, Gijon, Spain
Casado, LF:
Hosp Virgen Salud, Toledo, Spain
Gonzalez-Rodriguez, AP:
Hosp Univ Cent Asturias, Oviedo, Spain
Lopez-Anglada, L:
Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain
Puig, N:
Hosp Univ Salamanca, Inst Invest Biomed Salamanca, Salamanca, Spain
Cedena, MT:
Hosp 12 Octubre, Madrid, Spain
Paiva, B:
Clin Univ Navarra, Ctr Invest Med Aplicada CIMA, CIBERONC, IDISNA,CCUN, Pamplona, Spain
Mateos, MV:
Hosp Univ Salamanca, Inst Invest Biomed Salamanca, Salamanca, Spain
San-Miguel, J:
Clin Univ Navarra, Ctr Invest Med Aplicada CIMA, CIBERONC, IDISNA,CCUN, Pamplona, Spain
Lahuerta, JJ:
Hosp 12 Octubre, Madrid, Spain
Blade, J:
Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain
Troconiz, IF:
Univ Navarra, Fac Farm & Nutr, Pamplona, Spain
hybrid, Green Published
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