Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (851 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A lymphoproliferative disorder characterized by pleomorphic b-lymphocytes including plasma cells, with increased levels of monoclonal serum immunoglobulin M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include anemia; hemorrhages; and hyperviscosity.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Macroglobulinemia, Waldenstrom; Lymphoma, Lymphocytic, Plasmacytoid; Lymphoma, Lymphoplasmacytoid; Lymphomas, Lymphoplasmacytoid; Lymphoplasmacytoid Lymphoma; Lymphoplasmacytoid Lymphomas; Macroglobulinemia; Primary Macroglobulinemia.
Where it fits in the MeSH classification
- Broader topics
- Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Lymphoproliferative Disorders
Related concepts
- B-Lymphocytes
- Plasma Cells
- Immunoglobulin
- Anemia
- Hemorrhages
Research landscape
PubMed indexes 6,070 records tagged with the MeSH heading “Waldenstrom Macroglobulinemia” (counts retrieved 2026-10-29). 673 of them (11.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,643 records.
Reviews account for 779 records (12.8%) and meta-analyses for 5. Randomized controlled trials number 27 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,643 |
| 2000-2009 | 715 |
| 2010-2019 | 1,039 |
| 2020 onward | 673 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 779 | 12.8% |
| Meta-analyses | 5 | 0.1% |
| Randomized controlled trials | 27 | 0.4% |
Method: PubMed query "Waldenstrom Macroglobulinemia"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in cancer and oncology
Cancer research spans very different kinds of evidence. Laboratory studies in cell lines and animal models reveal mechanisms but often do not translate to patients. Early-phase trials mainly test safety and dosing, while phase 3 randomized trials and their meta-analyses are the usual basis for treatment conclusions. Outcomes also differ in meaning: tumour shrinkage, progression-free survival and overall survival are not interchangeable, and screening studies can be distorted by lead-time and overdiagnosis. When reading a result, check the cancer type and stage studied, the comparison treatment, and which outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study | 2023 | Randomized controlled trial Design not recorded in structured metadata | 101 | cc by PMID 37478390 · DOI · PMC10666987 |
| CXCR4 in Waldenström's Macroglobulinema: chances and challenges | 2021 | Review article Design not recorded in structured metadata | 76 | cc by PMID 33273682 · DOI · PMC7862063 |
| Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia | 2022 | Research article Design not recorded in structured metadata | 58 | cc by PMID 34531537 · DOI · PMC8807393 |
| Renal dysfunction in symptomatic Waldenström macroglobulinaemia: A nationwide Italian multicentre study | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 41796393 · DOI · PMC13267470 |
Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM).
- Closing excerpt
- Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (220 words)
The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM). Here, we report long-term follow-up outcomes from ASPEN. The primary end point was the sum of very good partial response (VGPR) + complete response (CR) rates; secondary and exploratory end points were also reported. Cohort 1 comprised 201 patients (myeloid differentiation primary response 88-mutant WM: 102 receiving zanubrutinib; 99 receiving ibrutinib); cohort 2 comprised 28 patients (myeloid differentiation primary response 88 wild-type WM: 28 zanubrutinib; 26 efficacy evaluable). At 44.4-month median follow-up, VGPR + CR rates were 36.3% with zanubrutinib versus 25.3% with ibrutinib in cohort 1 and 30.8% with one CR in cohort 2. In patients with CXC motif chemokine receptor 4 mutation, VGPR + CR rates were 21.2% with zanubrutinib versus 10.0% with ibrutinib (cohort 1). Median progression-free survival and overall survival were not reached. Any-grade adverse events (AEs) of diarrhea (34.7% v 22.8%), muscle spasms (28.6% v 11.9%), hypertension (25.5% v 14.9%), atrial fibrillation/flutter (23.5% v 7.9%), and pneumonia (18.4% v 5.0%) were more common with ibrutinib versus zanubrutinib; neutropenia (20.4% v 34.7%) was less common with ibrutinib versus zanubrutinib (cohort 1). Zanubrutinib was associated with lower risk of AE-related treatment discontinuation. Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37478390 · DOI · PMC10666987
CXCR4 in Waldenström's Macroglobulinema: chances and challenges [2]
Abstract reading summary — source excerpts
- Opening excerpt
- It is one of the major aims in cancer research to improve our understanding of the underlying mechanisms which initiate and maintain tumor growth and to translate these findings into novel clinical diagnostic and therapeutic concepts with the ultimate goal to improve patient care.
- Closing excerpt
- Well known for its central role in cancer progression and distribution, CXCR4 is highlighted in this review with regard to its biology, prognostic and predictive relevance and therapeutic implications in WM.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (240 words)
It is one of the major aims in cancer research to improve our understanding of the underlying mechanisms which initiate and maintain tumor growth and to translate these findings into novel clinical diagnostic and therapeutic concepts with the ultimate goal to improve patient care. One of the greater success stories in this respect has been Waldenström's Macroglobulinemia (WM), which is an incurable B-cell neoplasm characterized by serum monoclonal immunoglobulin M (IgM) and clonal lymphoplasmacytic cells infiltrating the bone marrow. Recent years have succeeded to describe the molecular landscape of WM in detail, highlighting two recurrently mutated genes, the MYD88 and the CXCR4 genes: MYD88 with an almost constant and recurrent point mutation present in over 90% of patients and CXCR4 with over 40 different mutations in the coding region affecting up to 40% of patients. Intriguingly, both mutations are activating mutations leading in the case of CXCR4 to an indelible activation and perpetual signaling of the chemokine receptor. These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases. Well known for its central role in cancer progression and distribution, CXCR4 is highlighted in this review with regard to its biology, prognostic and predictive relevance and therapeutic implications in WM.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33273682 · DOI · PMC7862063
Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM).
- Closing excerpt
- CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)
Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). With a median follow-up of 50 months, the overall, major, and VGPR response rates were 100%, 87%, and 30%. The VGPR rate was numerically but not significantly lower in patients with than without CXCR4 mutations (14% vs. 44%; p = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though were longer in those with mutated CXCR4 at 1.7 months (p = 0.07) and 7.3 months (p = 0.01). Six patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; p = 0.06). The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma. Atrial fibrillation occurred in 20% of patients. Ibrutinib monotherapy induced durable responses in treatment-naive patients with WM. CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34531537 · DOI · PMC8807393
Renal dysfunction in symptomatic Waldenström macroglobulinaemia: A nationwide Italian multicentre study [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The prognostic significance of impaired renal function in Waldenström macroglobulinaemia (WM) remains poorly defined.
- Closing excerpt
- Thus, renal dysfunction at diagnosis may represent an underrecognized, independent adverse prognostic factor in symptomatic WM.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (192 words)
The prognostic significance of impaired renal function in Waldenström macroglobulinaemia (WM) remains poorly defined. We conducted a nationwide multicentre study to evaluate its clinical characteristics and prognostic impact in symptomatic patients. We analysed 402 symptomatic WM patients, stratified according to renal function at diagnosis (creatinine clearance 2). Renal dysfunction was identified in 119 patients (29.6%). Renal biopsy was performed in 33 cases. Patients with reduced renal function were older (median age 76 vs. 67 years, p < 0.0001), had lower haemoglobin levels (10.8 vs. 11.8 g/dL, p = 0.008) and higher 24-h proteinuria (0.29 vs. 0.20 g, p = 0.04). Comorbidities of renal interest were similarly distributed between groups. Renal dysfunction was associated with inferior median overall survival (139 vs. 203 months, p < 0.001) and progression-free survival (PFS) (80 vs. 106 months, p = 0.002). Among patients aged <70 years, renal dysfunction remained associated with shorter PFS (77 vs. 121 months, p = 0.005). Importantly, worsening renal function did not correlate with increasing age. In this setting, first-line chemoimmunotherapy was associated with improved median PFS. Thus, renal dysfunction at diagnosis may represent an underrecognized, independent adverse prognostic factor in symptomatic WM.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41796393 · DOI · PMC13267470
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Waldenström's macroglobulinemia: clinical features, complications, and management [5]
- Research article Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases [6]
- Research article Genomic Landscape of Waldenström Macroglobulinemia and Its Impact on Treatment Strategies [7]
- Research article How I treat Waldenström macroglobulinemia [8]
- Research article Diagnosis and management of Waldenstrom's macroglobulinemia [9]
- Research article Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia [10]
References
- Dimopoulos MA, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, et al.. Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study. . 2023. PMID 37478390 · DOI · PMC10666987
- Kaiser LM, Hunter ZR, Treon SP, Buske C. CXCR4 in Waldenström's Macroglobulinema: chances and challenges. . 2021. PMID 33273682 · DOI · PMC7862063
- Castillo JJ, Meid K, Gustine JN, Leventoff C, White T, Flynn CA, et al.. Long-term follow-up of ibrutinib monotherapy in treatment-naive patients with Waldenstrom macroglobulinemia. . 2022. PMID 34531537 · DOI · PMC8807393
- Danesin N, Autore F, Frustaci AM, Favrin G, Cencini E, Noto A, et al.. Renal dysfunction in symptomatic Waldenström macroglobulinaemia: A nationwide Italian multicentre study. . 2026. PMID 41796393 · DOI · PMC13267470
- Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenström's macroglobulinemia: clinical features, complications, and management. J Clin Oncol. 2000. PMID 10623712 · DOI
- García-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A, et al.. Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol. 2001. PMID 11736938 · DOI
- Treon SP, Xu L, Guerrera ML, Jimenez C, Hunter ZR, Liu X, et al.. Genomic Landscape of Waldenström Macroglobulinemia and Its Impact on Treatment Strategies. J Clin Oncol. 2020. PMID 32083995 · DOI · PMC7351339
- Treon SP. How I treat Waldenström macroglobulinemia. Blood. 2009. PMID 19617573 · DOI
- Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom's macroglobulinemia. J Clin Oncol. 2005. PMID 15735132 · DOI
- Castillo JJ, Advani RH, Branagan AR, Buske C, Dimopoulos MA, D'Sa S, et al.. Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol. 2020. PMID 33091356 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.