hematology and oncology
Macroglobulinemia
Treatment of Macroglobulinemia
Plasma exchange (only when hyperviscosity is present or prior torituximabfor patients with high IgM levels) Corticosteroids, alkylating drugs, nucleoside analogs, monoclonal antibodies (especiallyrituximab) Chemotherapy, especially the alkylating agentbendamustinein combination withrituximab Other drugs, including proteasome inhibitors (bortezomiborcarfilzomib), immunomodulatory agents (thalidomide,pomalidomide, orlenalidomide), Bruton's tyrosine kinase (BTK) inhibitors (eg,ibrutinib) alone or in combination withrituximab, phosphoinositide 3-kinase (PI3) inhibitors (eg,idelalisib), or a mammalian target of rapamycin (mTOR) inhibitor (eg,everolimus) 60 years, anemia, and cryoglobulinemia predict shorter survival (for review, see Treatment references ). Often, patients require no treatment for many years Treatment references . If hyperviscosity is present, initial treatment is Corticosteroids may be effective in reducing the tumor load. Treatment with oral alkylating drugs may be indicated for palliation, but bone marrow toxicity can occur. Nucleoside analogs (fludarabineand 2-chlorodeoxyadenosine) produce responses in large numbers of newly diagnosed patients but have been associated with a high risk of myelodysplasia and myeloid leukemia. Rituximabcan reduce tumor burden without suppressing normal hematopoiesis. However, during the first several months, IgM levels may increase, requiring plasma exchange. The combination of this monoclonal antibody withbendamustineis highly effective. The proteasome inhibitorsbortezomibandcarfilzomiband the immunomodulating agentsthalidomide,lenalidomide, andpomalidomideare also effective in this cancer. BTK inhibitors, includingibrutinib,acalabrutinib, andzanubrutinib, have shown high levels of activity.Acalabrutinibandzanubrutinibcause less toxicity thanibrutinib.MYD88andCXCR4mutational status can predict the likelihood of response to these drugs. has shown significant clinical activity ( Treatment references ). Two other classes of drugs, PI3 kinase inhibitors such asidelalisib, and mTOR inhibitors, includingeverolimus, have been used effectively for previously treated patients. 1.Oza A, Rajkumar SV: Waldenstrom macroglobulinemia: Prognosis and management.Blood Cancer J5(3):e296, 2015. doi: 10.1038/bcj.2015.28 2.Castillo JJ, Allan JN, Siddiqi T, et al.Venetoclaxin Previously Treated Waldenström Macroglobulinemia.J Clin Oncol2022;40(1):63-71. doi:10.1200/JCO.21.01194 