Idelalisib plus rituximab is effective in systemic AL amyloidosis secondary to chronic lymphocytic leukaemia

Abstract

Light chain amyloidosis is characterized by the progressive deposition of immunoglobulin light chains into the extracellular tissue, leading to organ dysfunction. Usually, it is associated with an underlying clonal plasma cell dyscrasia and rarely with chronic lymphocytic leukaemia. Herein, we described the first report of a patient with relapsed chronic lymphocytic leukaemia harbouring TP53 abnormalities who developed, histologically proven, systemic light chain amyloidosis who was treated with the PI3K inhibitor, idelalisib, and rituximab. Unfortunately, the patient had sudden death during sleep, likely caused by arrhythmia secondary to amyloid cardiomyopathy. Idelalisib was at least effective in reducing secretory free light chain, chronic lymphocytic leukaemia burden, and to improve the survival of patient.

Peripheral nervous system involvement in lymphomas

“…Biological features are associated with the different clinical expression of CLL/SLL: in the indolent cases, no genetic abnormalities in the tumor suppressor gene TP53 and no mutated immunoglobulin heavy‐chain gene are usually found, whereas in the aggressive cases, TP53 gene abnormalities and/or complex karyotypes are typically detected . Common etiologies of neuropathy in CLL are viral (varicella zoster virus, VZV; hepatitis C virus, HCV), iatrogenic (ibrutinib, lenalidomide), immune‐mediated, idiopathic, rarely due to peripheral nerve invasion by leukemic cells or light chain amyloidosis . We have recently reported on a cohort of 816 CLL patients, 19 (2.2%) of whom had neuropathy.…”

“…12,14 Common etiologies of neuropathy in CLL are viral (varicella zoster virus, VZV; hepatitis C virus, HCV), iatrogenic (ibrutinib, lenalidomide), immune-mediated, idiopathic, rarely due to peripheral nerve invasion by leukemic cells 15,16 or light chain amyloidosis. 17 We have recently reported on a cohort of 816 CLL patients, 19 (2.2%) of whom had neuropathy. After excluding diabetic and iatrogenic neuropathy, in 12 of 816 patients (1.5%), other identifiable causes of neuropathy had been ruled out.…”

Educational Case: Orbital B-Cell Lymphoma With Amyloid Deposition

“…Treatment with rituximab, a monoclonal antibody against CD20, particularly in combination with other agents such as idelalisib, has shown efficacy in systemic AL. 39 An echocardiogram was performed, which showed no evidence of restrictive cardiomyopathy.…”

Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

“…After the demonstration of amyloid deposits by Congo red staining, amyloid typing with immunocytochemistry and identification of amyloid fibrils on electron microscopy should be used to formulate the correct diagnosis and start proper therapy. Sometimes, when the coexistence of the two conditions cannot be excluded a priori electron microscopy or immunohistochemistry are mandatory to identify the fibrils' composition [47,48].…”