Serum free light chains in a racially diverse population including African Americans and populations from South Africa
Abstract
Abstract Detection of light chain (LC) monoclonal gammopathies (MGs) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10 035 individuals for heavy chain MG, identifying 9028 negative cases whose FLC were measured. Participants included 4149 from the PROMISE study (United States, n = 2383; South Africa, n = 1766) and 4879 from the Mass General Brigham Biobank, with 44% self-identifying as Black. Using standard FLC reference ranges, 1074 of 10 035 individuals (10.7%) were diagnosed with LC monoclonal gammopathy of undetermined significance (MGUS), with 99% being κ-restricted. In the United States, 14.8% of Black and 4% of White individuals were diagnosed (P < .01). Among US participants of African (AFR) and European (EUR) genetic ancestry, 14.4% AFR and 2.9% EUR were diagnosed (P < .01). Among South Africans (100% Black), 27.8% were diagnosed using standard ranges. To avoid overdiagnosis, we propose a new κ/λ ratio reference range (0.686 to 2.10) for populations of AFR descent with normal renal function, with standard values for κ and λ being 7.97 to 77.50 mg/L and 6.20 to 49.20 mg/L, respectively. This reduces LC-MGUS overdiagnosis by 91% (10.7% vs 0.97%). Using the new reference, LC-MGUS accounts for 8.8% of MGUS cases, with 74% being κ-restricted, consistent with LC myeloma rates. These findings highlight the importance of basing disease definitions, such as MGUS, on diverse populations. Adopting our proposed FLC reference values would reduce MGUS overdiagnosis among Black individuals, avoiding unnecessary financial, psychological, and medical consequences. This study includes data from NCT03689595.
Article Details
Authors (28)
Luca Bertamini
Jean-Baptiste Alberge
David J. Lee
Habib El-Khoury
Sungjae Kim
1Dana-Farber Cancer Institute, Boston, United States
Grace Fleming
1Dana-Farber Cancer Institute, Boston, United States
Ciara Murphy
1Dana-Farber Cancer Institute, Boston, United States
Julia Colchie
1Dana-Farber Cancer Institute, Boston, United States
Maya I. Davis
1Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Jacqueline Perry
Elizabeth D. Lightbody
Sabine Allam
1Dana-Farber Cancer Institute, Boston, United States
Lindokuhle N. Goqwana
5Division of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
Vinitha Philip
6Clinical Haematology Unit, Department of Medicine, Faculty of Health Sciences, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa
Natalie Smyth
Dhananjay Sakrikar
9The Binding Site, a part of ThermoFisher Scientific, Boston, United States
Mark Perkins
9Binding Site Group, Part of Thermo Fisher Scientific, Birmingham, United Kingdom
Stephen Harding
2The Binding Site (part of Thermo Fisher Scientific), Birmingham, United Kingdom
Derek Troske
9The Binding Site, a part of ThermoFisher Scientific, Boston, United States
Gad Getz
Elizabeth W. Karlson
Nikhil Munshi
3VA Boston Healthcare System, Boston, MA
Kenneth C. Anderson
Lorenzo Trippa
From Médecins Sans Frontières (L.G., F.V.), Sorbonne Université, INSERM Unité 1135, Centre d’Immunologie et des Maladies Infectieuses (L.G.), Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié–Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (L.G.), and Epicentre (M.G., E. Baudin), Paris, and Translational Research on HIV and Endemic and Emerging Infectious Diseases, Montpellier Université de Montpellier, Montpellier, Institut de Recherche pour le Développement, Montpellier, INSERM, Montpellier (M.B.) — all in France; Interactive Development and Research, Singapore (U.K.); McGill University, Epidemiology, Biostatistics, and Occupational Health, Montreal (U.K.); UCSF Center for Tuberculosis (G.E.V., P.N., P.P.J.P.) and the Division of HIV, Infectious Diseases, and Global Medicine (G.E.V.), University of California at San Francisco, San Francisco; the National Scientific Center of Phth...
Catherine R. Marinac
1Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Wenlong C. Chen
Maureen Joffe
Irene M. Ghobrial