Abstract
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). BTK is a nonreceptor kinase involved in B-cell survival, proliferation, and interaction with the microenvironment. 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.
Highlights
Referred to as primary amyloidosis, immunoglobulin light chain amyloidosis (AL) is a clonal plasma cell proliferative disorder characterized by tissue deposits of immunoglobulin light chain fragments, leading to organ dysfunction [1]
As first reported by Chakraborty et al, 71% (10 out of 14) of patients harbored an MYD88 mutation; these patients had a different clinical outcome compared to others with an MYD88 wild type [9]. is mutation is found in 90% of cases of Waldenstrom’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma, and Advances in Hematology the MYD88 L265P mutation is associated with a higher risk of disease progression but a better response to Bruton’s tyrosine kinase inhibitors (BTKIs) therapy compared to others with wild-type MYD88
Ibrutinib has been approved for the treatment of chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and WM
Summary
Referred to as primary amyloidosis, immunoglobulin light chain amyloidosis (AL) is a clonal plasma cell proliferative disorder characterized by tissue deposits of immunoglobulin light chain fragments, leading to organ dysfunction [1]. In this Institutional Review Board approved protocol of Cleveland Clinic, we retrospectively evaluated the effects of BTK inhibitors ibrutinib and acalabrutinib therapy in patients (n 4) with IgM-related AL amyloidosis due to underlying WM.
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