Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management

Abstract

Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity.Diagnosis: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis.Risk Stratification: Age, hemoglobin level, platelet count, β 2 microglobulin, LDH, and monoclonal IgM concentrations are characteristics that are predictive of outcomes.Risk-Adapted Therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or a BTK inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib. Management of RefractoryDisease: Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection. 1 | PATIENT A 55-year-old male was found to have an IgM monoclonal gammopathy in January 2005. He was observed until November 2010 when his IgM level climbed to 9135 mg/dl. He was treated with rituximab, bortezomib, and dexamethasone for 4 months. Treatment was interrupted due to neuropathy, but the IgM level fell to 1150. He was observed until April 2015. At the time of progression his IgM was 11 500 mg/dl and he was found to have acquired von Willebrand disease. 1 He was treated with single-agent rituximab which failed to produce a minor response. He received bendamustine, lenalidomide, and rituximab with a response of <1 year. In 2018 he was placed on an experimental trial of oprozomib with a response of 5 years duration. At relapse in August of 2022, he was placed on a trial of ixazomib and ibrutinib. Ixazomib was poorly tolerated due to diarrhea, and he continued ibrutinib alone and has achieved a very good partial response.

Clinicopathological characteristics and prognosis in patients with monoclonal gammopathy and renal damage in central China: a multicenter retrospective cohort study

“…In contrast to MGUS, which does not require treatment 15 , clone-directed therapy is recommended for patients with MGRS to preserve renal function and reduce the risk of MGRS recurrence after renal transplantation 16 . Clone-directed therapy is also used in the treatment of MM, WM, and other hematologic cancers 17 , 18 , but has significant negative effects and is typically costly. Therefore, understanding the relationship between renal damage and MG is necessary.…”

Monoclonal gammopathy of renal significance: An atypical presentation of Waldenström’s disease

“…There is currently no standard treatment approach [ 5 , 6 , 12 ]. Plasmapheresis is often used in patients with symptoms of hyperviscosity or cryoglobulinemia, until systemic therapy successfully lowers the tumor mass and reduces the IgM protein concentration in the serum [ 13 ]. The systemic therapy includes different combinations of corticosteroids, alkylating agents, rituximab, proteasome inhibitors, or autotransplantation of hematopoietic progenitors.…”

“…The systemic therapy includes different combinations of corticosteroids, alkylating agents, rituximab, proteasome inhibitors, or autotransplantation of hematopoietic progenitors. Rituximab-based immunochemotherapy regimens were the mainstay of treatment for first-line and relapsed/refractory WD, but promising new therapies such as Bruton’s tyrosine kinase inhibitor (BTKi) or bendamustine have been developed with favorable safety and efficacy profiles [ 5 , 6 , 10 , 13 , 14 , 15 ].…”

A Phase II Study to Evaluate the Efficacy of Bortezomib in Combination with Thalidomide in Treatment-Naïve Waldenstrom Macroglobulinemia Patients

“…Waldenstrom macroglobulinemia (WM) is defined as lymphoplasmacytic lymphoma (LPL) associated with IgM monoclonal gammopathy, irrespective of the M protein size [ 1 , 2 ]. The treatment of goal of WM is to control disease without compromising quality of life by treatment-related adverse events (AEs) [ 3 , 4 ].…”