Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 22; no. 9; pp. e844 - e852
• Main 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, 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, Maria-Victoria, San-Miguel, Jesús, Lahuerta, Juan-José, Bladé, Joan, Trocóniz, Iñaki F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2022
• Subjects: Depht of response; Early treatment failure; Newly diagnosed myeloma; Prognostic marker; Time to best response; Time to best response; Newly diagnosed myeloma; Early treatment failure; Depht of response; Prognostic marker
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2022.04.024

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]).
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.
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.
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.
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).