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.
CITATION Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):e844-e852. doi: 10.1016/j.clml.2022.04.024. Epub 2022 May 5.