Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance-Like Phenotype in Patients With Monoclonal Gammopathies
Leire Burgos 1 , Luis-Esteban Tamariz-Amador 1 , Noemi Puig 2 , Maria-Teresa Cedena 3 , Camila Guerrero 1 , Tomas Jelínek 4 , Sarah Johnson 5 , Paolo Milani 6 , Lourdes Cordon 7 , Jose J Perez 2 , Marta Lasa 1 , Rosalinda Termini 1 , Albert Oriol 8 , Miguel-Teodoro Hernandez 9 , Luis Palomera 10 , Rafael Martinez-Martinez 11 , Javier de la Rubia 12 , Felipe de Arriba 13 , Rafael Rios 14 , Maria-Esther Gonzalez 15 , Mercedes Gironella 16 , Valentin Cabañas 17 , Maria Casanova 18 , Isabel Krsnik 14 , Albert Perez-Montaña 19 , Verónica González-Calle 2 , Paula Rodriguez-Otero 1 , Vladimir Maisnar 20 , Roman Hajek 4 , Fritz Van Rhee 5 , Victor Jimenez-Zepeda 21 , Giovanni Palladini 6 , Giampaolo Merlini 6 , Alberto Orfao 22 , Javier de la Cruz 3 , Joaquin Martinez-Lopez 3 , Juan-Jose Lahuerta 3 , Laura Rosiñol 23 , Joan Blade 23 , Maria-Victoria Mateos 2 , Jesus F San-Miguel 1 , Bruno Paiva 1 ; PETHEMA/GEM Cooperative Group
Purpose: The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated.
Patients and methods: An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis.
Results: Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival.
Conclusion: We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.
CITATION J Clin Oncol. 2023 Mar 17;JCO2201916. doi: 10.1200/JCO.22.01916