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Waldenstrom macroglobulinemia

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:1168
Name:Waldenstrom macroglobulinemia
Associated with:1 target
2 immuno-relevant ligands
Synonyms
lymphoplasmacytic lymphoma | Macroglobulinemia, Waldenstrom, somatic included | Macroglobulinemia, Waldenstrom, susceptibility to, 1 | WM
Description
A malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein
Database Links
Disease Ontology: DOID:0050747
OMIM: 153600
Orphanet: ORPHA33226

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
CXCR4
Comments:  Gene mutations that cause truncation of the cytoplasmic tail domain of the CXCR4 protein are associated with Waldenstrom macroglobulinemia.
References:  1
Mutations:  CXCR4 is associated with 4 mutation. Click here for details

Ligands

GtoPdb Disease Summaries - Ligands

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  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
ibrutinib
Immuno Disease Comments: Approved drug for WM.
Clinical Use: Ibrutinib is approved to treat patients with mantle cell lymphoma (MCL), a rare and aggressive type of leukemia, especially patients with MCL who have received at least one prior therapy. In Feb 2014 ibrutinib was granted US FDA approval for treating chronic lymphocytic leukemia (CLL), as with MCL, this is only indicated for patients who have received at least one prior therapy. In February 2015, the US FDA expanded approval to include the treatment of Waldenström's macroglobulinemia (WM), which is a form of type of non-Hodgkin's lymphoma. Approval was granted based on the outcome of clinical trial NCT01614821 which indicated that the drug can offer a substantial improvement over contemporary therapies.
In August 2017, the FDA expanded approval to include treatment of chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy (e.g. first-line corticosteroid therapy). This approval followed results from clinical trial NCT02195869. The recommended dose of ibrutinib for cGVHD is 420 mg, orally once daily. | View clinical data
zanubrutinib
Immuno Disease Comments: Phase 3 clinical candidate for WM- NCT03332173 will evaluate clinical efficacy of single agent BGB-3111 in patients with relapsed/refractory WM.
Clinical Use: Zanubrutinib was evaluated for efficacy in a large number of clinical trials, across a range of hematological cancers. Click here to link to ClinicalTrials.gov's full list of zanubrutinib/BGB-3111 studies.
The FDA first approved zanubrutinib in November 2019 for the treatment of mantle cell lymphoma (MCL; in adult patients who have received at least one prior therapy). In June 2020, the drug was approved in China for the treatment of adult patients with CLL/SLL who have received at least one prior therapy, and for patients with MCL who have received at least one prior therapy. In the EU, zanubrutinib holds orphan designation for lymphoplasmacytic lymphoma, which was granted in May 2019. In April 2021, the The FDA accepted a supplemental new drug application (sNDA) for zanubrutinib for the treatment of adults with Waldenström macroglobulinemia, and approval followed in August that year. FDA approval was expanded in early 2023, to include treatment of CLL, based on evidence from the phase 3 SEQUOIA study (NCT03336333) [2-3]. A further expansion by the FDA in March 2024 added the treatment of relapsed/refractory follicular lymphoma to zanubrutinib's indication list. | View clinical data
Bioactivity Comments: In a cellular assay, zanubrutinib inhibits BTK with an IC50 of 20nM [4]. | View biological activity

References

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1. Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Manning RJ, Tripsas C, Patterson CJ, Sheehy P et al.. (2014) The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood, 123 (11): 1637-46. [PMID:24366360]

2. Tam CS, Brown JR, Kahl BS, Ghia P, Giannopoulos K, Jurczak W, Šimkovič M, Shadman M, Österborg A, Laurenti L et al.. (2022) Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol, 23 (8): 1031-1043. [PMID:35810754]

3. Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, Simpson D, Shadman M, Ganly PS, Laurenti L et al.. (2020) Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Haematologica, 106 (9): 2354-2363. [PMID:33054121]

4. Wang Z, Guo Y. (2016) Substituted pyrazolo[1,5-a]pyrimidines as bruton's tyrosine kinase modulators. Patent number: US9447106B2. Assignee: Beigene Ltd.. Priority date: 25/04/2013. Publication date: 20/09/2016.