Laboratory practice is central to earlier myeloma diagnosis: Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services.
earlier diagnosis
laboratory practice
myeloma
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
02 Jan 2024
02 Jan 2024
Historique:
revised:
13
10
2023
received:
14
08
2023
accepted:
13
11
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
3
1
2024
Statut:
aheadofprint
Résumé
Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Myeloma UK
Informations de copyright
© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):538-548.
van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397(10272):410-427.
Cowan AJ, Allen C, Barac A, Basaleem H, Bensenor I, Curado MP, et al. Global burden of multiple myeloma: a systematic analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018;4:1221-1227.
Acquah ME, Hsing AW, McGuire V, Wang S, Birmann B, Dei-Adomakoh Y. Presentation and survival of multiple myeloma patients in Ghana: a review of 169 cases. Ghana Med J. 2019;53(1):52-58.
Kumar SK, Dimopoulos MA, Kastritis E, Terpos E, Nahi H, Goldschmidt H, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017;31:2443-2448.
Lyratzopoulos G, Neal RD, Barbiere JM, Rubin GP, Abel GA. Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England. Lancet Oncol. 2012;13(4):353-365.
Howell DA, Smith AG, Jack A, Patmore R, Macleod U, Mironska E, et al. Time-to-diagnosis and symptoms of myeloma, lymphomas and leukaemias: a report from the Haematological Malignancy Research Network. BMC Hematol. 2013;13:9.
Friese CR, Abel GA, Magazu LS, Neville BA, Richardson LC, Earle CC. Diagnostic delay and complications for older adults with multiple myeloma. Leuk Lymphoma. 2009;50(3):392-400.
Goldschmidt N, Zamir L, Poperno A, Kahan NR, Paltiel O. Presenting signs of multiple myeloma and the effect of diagnostic delay on the prognosis. J Am Board Fam Med. 2016;29(6):702-709.
Lacey K, Bishop JF, Cross HL, Chondros P, Lyratzopoulos G, Emery JD. Presentations to general practice before a cancer diagnosis in Victoria: a cross-sectional survey. Med J Aust. 2016;205(2):66-71.
Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM. 2007;100(10):635-640.
National Cancer Intelligence Network. Routes to Diagnosis 2006-2016 Workbook. 2016 [Cited 2021 Nov 13]. Available from: http://www.ncin.org.uk/publications/routes_to_diagnosis
Forbes LJ, Warburton F, Richards MA, Ramirez AJ. Risk factors for delay in symptomatic presentation: a survey of cancer patients. Br J Cancer. 2014;111(3):581-588.
Shephard EA, Neal RD, Rose P, Walter FM, Litt EJ, Hamilton WT. Quantifying the risk of multiple myeloma from symptoms reported in primary care patients: a large case-control study using electronic records. Br J Gen Pract. 2015;65(631):e106-e113.
Koo MM, Hamilton W, Walter FM, Rubin GP, Lyratzopoulos G. Symptom signatures and diagnostic timeliness in cancer patients: a review of current evidence. Neoplasia. 2018;20(2):165-174.
Atkin C, Iqbal G, Planche T, Pratt G, Yong K, Wood J, et al. Diagnostic pathways in multiple myeloma and their relationship to end organ damage: an analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) trial. Br J Haematol. 2021;192(6):997-1005.
Sive J, Cuthill K, Hunter H, Kazmi M, Pratt G, Smith D, et al. Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum Guideline. Br J Haematol. 2021;193(2):245-268.
Bence JH. Papers on chemical pathology, lecture III. Lancet. 1847;2:88-92.
Gally JA, Edelman GM. Physicochemical properties of Bence-Jones proteins in the form of l-chain dimmers. Biochim Biophys Acta. 1965;94:175-182.
Grey HM, Mannik M, Kunkel HG. Individual antigenic specificity of myeloma proteins. Characteristics and localization to subunits. J Exp Med. 1965;121:561-575.
Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47(4):673-680.
Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet. 2003;361(9356):489-491.
Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood. 2001;97(9):2900-2902.
Giles HV, Cook MA, Drayson MT, Cook G, Wright NJ, North SJ, et al. Redefining non-measurable multiple myeloma using mass spectrometry. Blood. 2022;139(6):946-950.
Chapman JR, Thoren KL. Tracking of low disease burden in multiple myeloma: using mass spectrometry assays in peripheral blood. Best Pract Res Clin Haematol. 2020;33(1):101142.
Heaney JLJ, Campbell JP, Griffin AE, Birtwistle J, Shemar M, Child JA, et al. Diagnosis and monitoring for light chain only and oligosecretory myeloma using serum free light chain tests. Br J Haematol. 2017;178(2):220-230.
Drayson M, Begum G, Basu S, Makkuni S, Dunn J, Barth N, et al. Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. Blood. 2006;108(6):2013-2019.
Royal V, Leung N, Troyanov S, Nasr SH, Écotière L, LeBlanc R, et al. Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study. Blood. 2020;135(21):1833-1846.
Hutchison CA, Batuman V, Behrens J, Bridoux F, Sirac C, Dispenzieri A, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol. 2011;8(1):43-51.
Hutchison CA, Cockwell P, Stringer S, Bradwell A, Cook M, Gertz MA, et al. Early reduction of serum-free light chains associates with renal recovery in myeloma kidney. J Am Soc Nephrol. 2011;22:1129-1136.
Hutchison CA, Bladé J, Cockwell P, Cook M, Drayson M, Fermand J, et al. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat Rev Nephrol. 2012;8(4):234-243.
Rana R, Pratt G, Cook M, Drayson MT, Ramasamy K, Sadler R, et al. Improving the diagnostic pathway in patients presenting with acute kidney injury secondary to de novo multiple myeloma: a short report. BMJ Open Qual. 2021;10(3):e001085.
Agbuduwe C, Iqbal G, Cairns D, Menzies T, Dunn J, Gregory W, et al. Clinical characteristics and outcomes of IgD myeloma: experience across UK national trials. Blood Adv. 2022;6(17):5113-5123.
Feyler S, O'Connor SJ, Rawstron AC, Subash C, Ross FM, Pratt G, et al. IgM myeloma: a rare entity characterized by a CD20-CD56-CD117- immunophenotype and the t(11;14). Br J Haematol. 2008;140(5):547-551.
Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24(6):1121-1127.
Rajkumar SV, Kyle RA, Therneau TM, Melton LJ III, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106(3):812-817.
Turesson I, Kovalchik SA, Pfeiffer RM, Kristinsson SY, Goldin LR, Drayson MT, et al. Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden. Blood. 2014;123(3):338-345.
Perez-Persona E, Mateo G, Garcia-Sanz R, Mateos MV, de Las Heras N, de Coca AG, et al. Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells. Br J Haematol. 2010;148(1):110-114.
Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378(3):241-249.
Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ III, Colby CL, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet. 2010;375(9727):1721-1728.
Therneau TM, Kyle RA, Melton LJ III, Larson DR, Benson JT, Colby CL, et al. Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition. Mayo Clin Proc. 2012;87(11):1071-1079.
Kristinsson SY, Bjorkholm M, Andersson TML, Eloranta S, Dickman PW, Goldin LR, et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study. Haematologica. 2009;94(12):1714-1720.
Fermand JP, Bridoux F, Dispenzieri A, Jaccard A, Kyle RA, Leung N, et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood. 2018;132(14):1478-1485.
Leung N, Bridoux F, Batuman V, Chaidos A, Cockwell P, D'Agati VD, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol. 2019;15(1):45-59.
Melton LJ 3rd, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA. Fracture risk in monoclonal gammopathy of undetermined significance. J Bone Miner Res. 2004;19(1):25-30.
Kristinsson SY, Pfeiffer RM, Bjorkholm M, Goldin LR, Schulman S, Blimark C, et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood. 2010;115(24):4991-4998.
Karlsson J, Andreasson B, Kondori N, Erman E, Riesbeck K, Hogevik H, et al. Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance. Clin Vaccine Immunol. 2011;18(6):969-977.
Gregersen H, Madsen KM, Sorensen HT, Schønheyder HC, Ibsen JS, Dahlerup JF. The risk of bacteremia in patients with monoclonal gammopathy of undetermined significance. Eur J Haematol. 1998;61(2):140-144.
Sigurdardottir EE, Turesson I, Lund SH, Lindqvist EK, Mailankody S, Korde N, et al. The role of diagnosis and clinical follow-up of monoclonal gammopathy of undetermined significance on survival in multiple myeloma. JAMA Oncol. 2015;1(2):168-174.
Go RS, Gundrum JD, Neuner JM. Determining the clinical significance of monoclonal gammopathy of undetermined significance: a SEER-Medicare population analysis. Clin Lymphoma Myeloma Leuk. 2015;15(3):177-186.
Atkin C, Richter A, Sapey E. What is the significance of monoclonal gammopathy of undetermined significance? Clin Med (Lond). 2018;18(5):391-396.
Tomasson MH, Ali M, De Oliveira V, Xiao Q, Jethava Y, Zhan F, et al. Prevention is the best treatment: the case for understanding the transition from monoclonal gammopathy of undetermined significance to myeloma. Int J Mol Sci. 2018;19(11):3621.
Rognvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, et al. Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies. Blood Cancer J. 2021;11(5):94.
Kristinsson SY, Rögnvaldsson S, Thorsteinsdottir S, Reed ER, Oskarsson JTT, Petursdottir I, et al. Screening for monoclonal gammopathy of undetermined significance: a population-based randomized clinical trial. First results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study (Abstract). Blood. 2021;138:156. https://doi.org/10.1182/blood-2021-152333
Ghobrial I. Predicting Progression of Developing Myeloma in a High-Risk Screened Population (PROMISE). Available from: https://www.clinicaltrials.gov/ct2/show/NCT03689595https://www.clinicaltrials.gov/ct2/show/NCT03689595
Heaney JLJ, Richter A, Bowcock S, Pratt G, Child JA, Jackson G, et al. Excluding myeloma diagnosis using revised thresholds for serum free light chain ratios and M-protein levels. Haematologica. 2020;105(4):e169-e171.
Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002;48(9):1437-1444.
Hutchison CA, Plant T, Drayson M, Cockwell P, Kountouri M, Basnayake K, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol. 2008;9:11. https://doi.org/10.1186/1471-2369-9-11
Myeloma: diagnosis and management NICE guideline [NG35]. 2016.
Willrich MAV, Murray DL, Kyle RA. Laboratory testing for monoclonal gammopathies: focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Clin Biochem. 2018;51:38-47.
Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2008;23(2):215-224.
Newsome PN, Cramb R, Davison SM, Dillon JF, Foulerton M, Godfrey EM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6-19.
Fernández-Ruiz M, López-Medrano F, Varela-Peña P, Lora-Pablos D, García-Reyne A, González E, et al. Monitoring of immunoglobulin levels identifies kidney transplant recipients at high risk of infection. Am J Transplant. 2012;12(10):2763-2773.
Hull RP, Goldsmith DJ. Nephrotic syndrome in adults. BMJ. 2008;336(7654):1185-1189.
Yuzawa Y, Yamamoto R, Takahashi K, Katafuchi R, Tomita M, Fujigaki Y, et al. Evidence-based clinical practice guidelines for IgA nephropathy 2014. Clin Exp Nephrol. 2016;20(4):511-535.
https://academy.myeloma.org.uk/resources/gp-myeloma-diagnostic-tool/
Caers J, Garderet L, Kortüm KM, O'Dwyer ME, van de Donk NWCJ, Binder M, et al. European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when. Haematologica. 2018;103(11):1772-1784.
Dejoie T, Corre J, Caillon H, Hulin C, Perrot A, Caillot D, et al. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma. Blood. 2016;128:2941-2948.
Fermand JP, Bridoux F, Kyle RA, Kastritis E, Weiss BM, Cook MA, et al. How I treat monoclonal gammopathy of renal significance (MGRS). Blood. 2013;122(22):3583-3590.
Gillmore JD, Wechalekar A, Bird J, Cavenagh J, Hawkins S, Kazmi M, et al. Guidelines on the diagnosis and investigation of AL amyloidosis. Br J Haematol. 2015;168(2):207-218.
Beetham R, Wassell J, Wallage MJ, Whiteway AJ, James JA. Can serum free light chains replace urine electrophoresis in the detection of monoclonal gammopathies? Ann Clin Biochem. 2007;44(Pt6):516-522.
Beetham R. Detection of Bence Jones protein in practice. Ann Clin Biochem. 2000;37:563-570.
Stern S, Chaudhuri S, Drayson M, Henshaw S, Karunanithi K, Willis F, et al. Investigation and management of the monoclonal gammopathy of undetermined significance (MGUS). A British Society for Haematology Good Practice Paper.
Go RS, Heien HC, Sangaralingham LR, Habermann EB, Shah ND. Estimating the risk of progression of monoclonal gammopathy of undetermined significance into lymphoplasmacytic malignancies in the United States: determining demographic differences using a national dataset [abstract]. Blood. 2016;128(22):843.