Humoral Immune Reconstitution with the Use of Bruton Tyrosine Kinase Inhibitor Treatment for Patients with Waldenström Macroglobulinemia

Background/Objectives: Waldenström macroglobulinemia (WM) is a B-cell lymphoma, defined by immunoglobulin M monoclonal gammopathy, lymphoplasmacytic marrow infiltration, and impaired humoral immunity with increased infections. With advances in WM treatment, Bruton tyrosine kinase inhibitors (BTKis) are increasingly used as first-line therapy. Studies show that BTKi use in chronic lymphocytic leukemia is associated with partial humoral immune reconstitution and decreased rates of infections. This study investigates whether BTKi treatment for WM is associated with a reduced risk of infectious complications compared with traditional systemic therapies. Methods: In this single-institution retrospective analysis, we compared immunoglobulin levels and infectious complications in WM patients treated with BTKis, rituximab, or chemoimmunotherapy. Results: Treatment of WM with BTKis was associated with an increase in serum IgA levels by 33%. Rituximab monotherapy was also associated with increased IgA (9%), but after 24 months. Patients treated with BTKis developed fewer infections, 50% compared with 68.4–71.4% of patients in other groups. Severe infections (≥grade 3) occurred most frequently in patients treated with chemoimmunotherapy. There was no correlation between development of infections and serum IgG levels or neutrophil count. Conclusions: Results demonstrate that treatment with BTKis is associated with a decreased risk of infection over time due to partial humoral immune reconstitution, as evidenced by increasing serum IgA.