Clinical presentation and treatment responses in IgM-related AL amyloidosis

Abstract

Amyloid light-chain (AL) amyloidosis is a multi-organ disease due to deposition of misfolded monoclonal immunoglobulin light chains. IgM AL amyloidosis is a rare variant, about 6% of AL amyloidosis cases, and more data are needed for treatment guidance. In IgM AL amyloidosis, the clonal cell of origin may be a plasma or lymphoplasmacytic cell, and treatments targeting each are employed. We describe presenting clinical and laboratory features of 95 patients with IgM AL amyloidosis treated at Boston University Amyloidosis Center from 1996 to 2012. The median diagnosis age was 66 years (range: 38-89) with 56% males. Organ involvement rates were: kidney (51%); heart (40%); lymph nodes (25%) and gastrointestinal tract (17%). Treatment responses were analyzed for 46 patients seen after 2003. Five treatment regimens were assigned by bone marrow pathology and patient-specific factors. Overall hematologic response rates and very good partial or complete hematologic response rates, respectively, were: high-dose melphalan/stem cell transplant (HDM/SCT) 100%;80%, Bortezomib 82%;27%, Rituximab 80%;27%, immunomodulatory agents (IMids) 75%;0%, and standard dose alkylating agents (Melphalan or cyclophosphamide) 63%;19%. Overall, 5-year survival rates were significantly higher in patients with a hematological response: 79.2 ± 8.5% versus 41 ± 14.9% in non-responders, which is more favorable than typically expected in AL amyloidosis.

<p>Treatment Options For Relapsed/refractory Systemic Light-Chain (AL) Amyloidosis: Current Perspectives</p>

“…Approximately 4-6% of patients with AL amyloidosis have an underlying IgM paraprotein associated with a lymphoplasmacytic bone marrow clone. Many of the same treatment regimens can be used with good success in these patients 49. Overall response rate to bortezomib is approximately 82%, immunomodulatory agents have a response rate of approximately 75%, and alkylating agents such as melphalan or cyclophosphamide have response rates of approximately 63%.…”

“…Overall response rate to bortezomib is approximately 82%, immunomodulatory agents have a response rate of approximately 75%, and alkylating agents such as melphalan or cyclophosphamide have response rates of approximately 63%. HDM/SCT is not frequently used in indolent lymphomas in the absence of AL amyloidosis, but the response rate in patients with AL amyloidosis and concurrent lymphoma has been reported as high as 100% 49. Despite these high overall response rates, the rates of complete response and very good partial responses are much lower and therefore other regimens that may be more effective in indolent lymphomas are often considered.…”

First report of MYD88L265P somatic mutation in IgM-associated light-chain amyloidosis

“…5 In our study, all but 1 MYD88 L265P -positive patient had clonal B lymphocyte in marrow, likely indicating association of MYD88 L265P mutation with LPDs. MYD88 L265P -positive patients had a lower rate of cardiac involvement (1/10; 10%), compared with an expected rate of 32% to 40% 14,15 in patients with IgM amyloidosis. On the other hand, a higher incidence of amyloid neuropathy (4/10; 40%) was seen in these patients.…”

Autologous Stem Cell Transplant for IgM-Associated Amyloid Light-Chain Amyloidosis

“…Amyloidosis related to an IgM monoclonal protein is a rare entity accounting for approximately 5% of patients with immunoglobulin amyloid light-chain (AL) amyloidosis [1,2]. Patients with IgM-related AL amyloidosis tend to present with lower levels of serum free light chains and have less cardiac involvement and more neurologic involvement compared with those with nonÀIgM-related AL amyloidosis [1][2][3]. Therapy is generally extrapolated form regimens used for nonÀIgM-related AL amyloidosis.…”