Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma
Luis-Esteban Tamariz-Amador 1 , Paula Rodríguez-Otero 2 , Ana Jiménez-Ubieto 3 , Laura Rosiñol 4 , Albert Oriol 5 , Rafael Ríos 6 , Anna Sureda 7 , Maria Jesus Blanchard 8 , Miguel Teodoro Hernández 9 , Valentin Cabañas Perianes 10 , Isidro Jarque 11 , Juan Bargay 12 , Mercedes Gironella 13 , Felipe De Arriba 14 , Luis Palomera 15 , Yolanda Gonzalez-Montes 16 , Josep M Martí 17 , Isabel Krsnik 18 , José María Arguiñano 19 , María Esther González 20 , Luis Felipe Casado 21 , Ana Pilar González-Rodriguez 22 , Lucía López-Anglada 4 , Noemi Puig 23 , Maria Teresa Cedena 3 , Bruno Paiva 24 , Maria-Victoria Mateos 23 , Jesús San-Miguel 24 , Juan-José Lahuerta 3 , Joan Bladé 4 , Iñaki F Trocóniz 25
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.