This Study Aims to Clarify the Prevalence and Characteristics of Neuropathy, Along With Associated Paraclinical Findings in Patients With Waldenström's Macroglobulinemia (WM) in a Cohort of WM Patients to Optimize the Diagnostic Process

NCT07160270 | Recruiting

• 1 other identifier: H-23064477
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Neuropathy severely reduces patients' quality of life due to sensory loss, chronic neuropathic pain, and loss of mobility of arms and legs. Given the diverse origins of neuropathy, it is critical to identify its specific causes, particularly when effective treatments are available. Neuropathy is a frequent morbidity in Waldenström's macroglobulinemia (WM), a specific type of lymphoma caused by infiltration of clonal lymphoplasmocytic B cells in the bone marrow with the presence of IgM paraprotein. WM associated neuropathy is largely undescribed. The few existing studies are mostly retrospective indicating the neuropathy has a heterogenic pathophysiology and diverse clinical appearance from mild sensory neuropathy to aggressive with loss of ambulation and development of chronic neuropathic pain within weeks to months. With treatment of WM the speed of the disease progression including the related neuropathy can be halted. Few studies and clinical experience indicate that the nerve damage induced by WM might remit if treatment is initiated early in the course of the disease. Thus, there is need for timely interventions to reduce chronic disabilities. However, even for an experienced neurologist, it can be difficult to identify whether the neuropathy is caused by WM or other causes where treatment is not indicated. This project aims to investigate the prevalence and underlying mechanisms of neuropathy in patients with WM to help speed up the diagnostic process and thus help slow down the irreversible nerve damage that these patients experience.

Conditions

Waldenstrom Macroglobulinaemia; Peripheral Neuropathies

Outcome Measures

Primary Outcomes (1)

• Prevalence of peripheral neuropathy associated to Waldenström Macroglobulinema (WM)

  The prevalence will be calculated by screening WM patients with a questionnaire designed specific for the research project to identify possible peripheral neuropathy. Patients with possible peripheral neuropathy will be clinical examined to either positiv og negative for peripheral neuropathy and confirmed by nerve conduction study. The prevalence will be the amount of patient with polyneuropathy in the population of investigated patientes with WM.

  From enrollment from August 2024 and new diagnosed patients with WM and symptoms of neuropathy refered to the neuromuscular clinic until July 2025.

Secondary Outcomes (1)

• Disability of WM associated polyneuropathy

  Investigation during one year with follow up for 3 years

Study Arms (1)

Neuropathy associated to Waldenström's Macroglobulinemia

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Active diagnose of Waldenström's Macroglobulinemia under follow-up or has been followed at Rigshospitalet Department of Hematology.

You may qualify if:

• Diagnosis of Waldenström's Macroglobulinemia with symptoms of peripheral neuropathy for further clinical investigation.

You may not qualify if:

• Investigated with no sign of peripheral neuropathy

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Copenhagen Neuromuscular Center, Rigshospitalet Blegdamsvej.

København Ø, 2100, Denmark

RECRUITING

Related Publications (14)

• Buske C, Castillo JJ, Abeykoon JP, Advani R, Arulogun SO, Branagan AR, Cao X, D'Sa S, Hou J, Kapoor P, Kastritis E, Kersten MJ, LeBlond V, Leiba M, Matous JV, Paludo J, Qiu L, Tam CS, Tedeschi A, Thomas SK, Tohidi-Esfahani I, Varettoni M, Vos JM, Garcia-Sanz R, San-Miguel J, Dimopoulos MA, Treon SP, Trotman J. Report of consensus panel 1 from the 11th International Workshop on Waldenstrom's Macroglobulinemia on management of symptomatic, treatment-naive patients. Semin Hematol. 2023 Mar;60(2):73-79. doi: 10.1053/j.seminhematol.2023.03.005. Epub 2023 Mar 29.

  PMID: 37099027 BACKGROUND

• D'Sa S, Kersten MJ, Castillo JJ, Dimopoulos M, Kastritis E, Laane E, Leblond V, Merlini G, Treon SP, Vos JM, Lunn MP. Investigation and management of IgM and Waldenstrom-associated peripheral neuropathies: recommendations from the IWWM-8 consensus panel. Br J Haematol. 2017 Mar;176(5):728-742. doi: 10.1111/bjh.14492. Epub 2017 Feb 15.

  PMID: 28198999 BACKGROUND

• Treon SP, Hanzis CA, Ioakimidis LI, Patterson CJ, Hunter ZR, Brodsky PS, m.fl. Clinical characteristics and treatment outcome of disease-related peripheral neuropathy in Waldenstrom's macroglobulinemia (WM). J Clin Oncol. 20. maj 2010;28(15_suppl):8114-8114.

  BACKGROUND

• Hanewinckel R, Drenthen J, van Oijen M, Hofman A, van Doorn PA, Ikram MA. Prevalence of polyneuropathy in the general middle-aged and elderly population. Neurology. 2016 Nov 1;87(18):1892-1898. doi: 10.1212/WNL.0000000000003293. Epub 2016 Sep 28.

  PMID: 27683845 BACKGROUND

• Dimopoulos MA, Kastritis E, Owen RG, Kyle RA, Landgren O, Morra E, Leleu X, Garcia-Sanz R, Munshi N, Anderson KC, Terpos E, Ghobrial IM, Morel P, Maloney D, Rummel M, Leblond V, Advani RH, Gertz MA, Kyriakou C, Thomas SK, Barlogie B, Gregory SA, Kimby E, Merlini G, Treon SP. Treatment recommendations for patients with Waldenstrom macroglobulinemia (WM) and related disorders: IWWM-7 consensus. Blood. 2014 Aug 28;124(9):1404-11. doi: 10.1182/blood-2014-03-565135. Epub 2014 Jul 15.

  PMID: 25027391 BACKGROUND

• Castillo JJ, D'Sa S, Lunn MP, Minnema MC, Tedeschi A, Lansigan F, Palomba ML, Varettoni M, Garcia-Sanz R, Nayak L, Lee EQ, Rinne ML, Norden AD, Ghobrial IM, Treon SP. Central nervous system involvement by Waldenstrom macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study. Br J Haematol. 2016 Mar;172(5):709-15. doi: 10.1111/bjh.13883. Epub 2015 Dec 21.

  PMID: 26686858 BACKGROUND

• Viala K, Stojkovic T, Doncker AV, Maisonobe T, Lenglet T, Bruneteau G, Musset L, Neil J, Leger JM, Leblond V. Heterogeneous spectrum of neuropathies in Waldenstrom's macroglobulinemia: a diagnostic strategy to optimize their management. J Peripher Nerv Syst. 2012 Mar;17(1):90-101. doi: 10.1111/j.1529-8027.2012.00376.x.

  PMID: 22462670 BACKGROUND

• Levine T, Pestronk A, Florence J, Al-Lozi MT, Lopate G, Miller T, Ramneantu I, Waheed W, Stambuk M, Stone MJ, Choksi R. Peripheral neuropathies in Waldenstrom's macroglobulinaemia. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):224-8. doi: 10.1136/jnnp.2005.071175.

  PMID: 16421127 BACKGROUND

• Tomkins O, Leblond V, Lunn MP, Viala K, Weil DR, D'Sa S. Investigation and Management of Immunoglobulin M- and Waldenstrom-Associated Peripheral Neuropathies. Hematol Oncol Clin North Am. 2023 Aug;37(4):761-776. doi: 10.1016/j.hoc.2023.04.007.

  PMID: 37385714 BACKGROUND

• Bibas M, Sarosiek S, Castillo JJ. Waldenstrom Macroglobulinemia - A State-of-the-Art Review: Part 1: Epidemiology, Pathogenesis, Clinicopathologic Characteristics, Differential Diagnosis, Risk Stratification, and Clinical Problems. Mediterr J Hematol Infect Dis. 2024 Jul 1;16(1):e2024061. doi: 10.4084/MJHID.2024.061. eCollection 2024.

  PMID: 38984103 BACKGROUND

• Racine M. Chronic pain and suicide risk: A comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Dec 20;87(Pt B):269-280. doi: 10.1016/j.pnpbp.2017.08.020. Epub 2017 Aug 26.

  PMID: 28847525 BACKGROUND

• Damci A, Schruers KRJ, Leue C, Faber CG, Hoeijmakers JGJ. Anxiety and depression in small fiber neuropathy. J Peripher Nerv Syst. 2022 Dec;27(4):291-301. doi: 10.1111/jns.12514. Epub 2022 Oct 7.

  PMID: 36168866 BACKGROUND

• Streckmann F, Balke M, Cavaletti G, Toscanelli A, Bloch W, Decard BF, Lehmann HC, Faude O. Exercise and Neuropathy: Systematic Review with Meta-Analysis. Sports Med. 2022 May;52(5):1043-1065. doi: 10.1007/s40279-021-01596-6. Epub 2021 Dec 29.

  PMID: 34964950 BACKGROUND

• Girach A, Julian TH, Varrassi G, Paladini A, Vadalouka A, Zis P. Quality of Life in Painful Peripheral Neuropathies: A Systematic Review. Pain Res Manag. 2019 May 23;2019:2091960. doi: 10.1155/2019/2091960. eCollection 2019.

  PMID: 31249636 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

For patients included in the study with verified peripheral neuropathy and no other known cause than the association to Waldenströms Macroglobulinemia will be offered a genetic test for hereditary neuropathies though whole genome sequencing.

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Peripheral Nervous System Diseases

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Morten Müller Aagaard, Medical Doctor

CONTACT

+4521671835; morten.mueller.aagaard.01@regionh.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: September 8, 2025
• Study Start: May 14, 2025
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-08

Locations

DK (1)