Management of Waldenstrom macroglobulinemia in 2020.

Article Details

Citation

Castillo JJ, Treon SP

Management of Waldenstrom macroglobulinemia in 2020.

Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):372-379. doi: 10.1182/hematology.2020000121.

PubMed ID
33275726 [ View in PubMed
]
Abstract

The management of Waldenstrom macroglobulinemia (WM) has evolved tremendously with recent genomic discoveries that correlate with clinical presentation and could help to tailor treatment approaches. The current diagnosis of WM requires clinicopathological criteria, including bone marrow involvement by lymphoplasmacytic lymphoma cells, a serum immunoglobulin M (IgM) monoclonal paraprotein, and presence of the MYD88 L265P mutation. Once the diagnosis is established, the relationship between the patient's symptoms and WM should be carefully investigated, because therapy should be reserved for symptomatic patients. Bone marrow involvement and serum levels of IgM, albumin, and beta2-microglobulin can be used to estimate the time until treatment initiation. The treatment of WM patients should be highly personalized, and the patient's clinical presentation, comorbidities, genomic profile, and preferences, as well as toxicity of the treatment regimens, should be taken into account. Alkylating agents (bendamustine, cyclophosphamide), proteasome inhibitors (bortezomib, carfilzomib, ixazomib), anti-CD20 monoclonal antibodies (rituximab, ofatumumab), and Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, zanubrutinib) are safe and highly effective treatment options in patients with WM. Because novel covalent and noncovalent BTK inhibitors (tirabrutinib, vecabrutinib, LOXO-305, ARQ-531), BCL2 antagonists (venetoclax), and CXCR4-targeting agents (ulocuplumab, mavorixafor) are undergoing clinical development in WM, the future of WM therapy certainly appears bright and hopeful.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MavorixaforC-X-C chemokine receptor type 4ProteinHumans
Unknown
Antagonist
Inhibitor
Details
TirabrutinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
UlocuplumabC-X-C chemokine receptor type 4ProteinHumans
Yes
Inhibitor
Details
VecabrutinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
VenetoclaxApoptosis regulator Bcl-2ProteinHumans
Yes
Antagonist
Inhibitor
Details