Utility of Bruton's Tyrosine Kinase Inhibitors in Light Chain Amyloidosis Caused by Lymphoplasmacytic Lymphoma (Waldenström's Macroglobulinemia)
Source : https://www.hindawi.com/journals/ah/2022/1182384/
Of the variety of immunoglobulin related amyloidosis (AL), immunoglobulin M (IgM) related AL represents only 6 to 10% of affected patients, and the majority of these cases are associated with underlying non-Hodgkin’s Lymphoma including Waldenström’s macroglobulinemia (WM). Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin’s lymphoma (NHL).
Conclusion/Relevance: We retrospectively evaluated the tolerability and effectiveness of BTK inhibitors ibrutinib and acalabrutinib therapy in (n = 4) patients with IgM-related AL amyloidosis with underlying WM. Treatment was well tolerated with both hematologic and organ response in patients with AL amyloidosis in the setting of WM. Atrial fibrillation led to the discontinuation of ibrutinib in one patient, and acalabrutinib caused significant thumb hematoma needing dose reduction in another patient. All patients evaluated had the MYD88 mutation. This may explain the good response to BTK inhibitors therapy in our series. BTK inhibitors should be further investigated in larger prospective studies for treatment of AL amyloidosis in patients with lymphoplasmacytic lymphoma/WM.
• Source: Advances in Hematology
• Conclusions: “All patients evaluated had the MYD88 mutation. This may explain the good response to BTK inhibitors therapy in our series. BTK inhibitors should be further investigated in larger prospective studies for treatment of AL amyloidosis in patients with lymphoplasmacytic lymphoma/WM.”
• Cleveland Clinic researchers reported outcomes of four patients treated with BTKIs (2 patients with ibrutinib and 2 with acalabrutinib) during 1L and 2L. The patients were treated due to IgM-related AL amyloidosis secondary to MYD88 mutated Waldenström macroglobulinemia (WM). They tolerated BTKIs well and hematologic responses and organ responses were “excellent,” per the investigators.
• One limitation of the study is it is small, retrospective, and single center. It does, however, bolster the notion that gingerly selecting patients can lead to successful treatment with ibrutinib and acalabrutinib for the treatment of systemic AL amyloidosis due to IgM-related AL amyloidosis secondary to MYD88 mutated WM. Another limitation was that CXCR4 mutation status was not available, and WM patients with CXCR4 mutations usually demonstrate inferior response to BTK inhibitors.
• “For this reason, BTK inhibitor therapy should not be considered the frontline therapy option in WM patients who are MYD88 wild-type and CXCR4 mutated. While selecting therapy for the treatment of newly diagnosed AL in the setting of WM, it is also important to note that frontline BTK inhibitor therapy is usually a long-term commitment and can be associated with side effects over time, as opposed to a fixed duration of 6 months or less treatment with chemoimmunotherapy such as bendamustine and rituximab (B-R),” wrote the authors.