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Waldenstrom macroglobulinemia

Disease ID:1168
Name:Waldenstrom macroglobulinemia
Associated with:1 target
2 immuno-relevant ligands
lymphoplasmacytic lymphoma | Macroglobulinemia, Waldenstrom, somatic included | Macroglobulinemia, Waldenstrom, susceptibility to, 1 | WM
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


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


Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
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
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'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


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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.