Clinical Presentation and Treatment Responses in IgM AL Amyloidosis, a Series of 106 Patients

Objective: AL amyloidosis is a multiorgan disease due to deposition of misfolded monoclonal immunoglobulin light chains. AL amyloidosis with IgM paraproteinemia is a rare variant of this disease; accounting for approximately 6% of AL amyloidosis cases. The clonal cell of origin may be a plasma cell or lymphoplasmacytic cell, and treatments targeting each have been employed. This study describes clinical and laboratory features of IgM AL amyloidosis patients and their response to different therapeutic regimens.

Methods: 106 patients with IgM-related AL amyloidosis were evaluated at the BUMC Amyloidosis Center during 1996-2012. Treatment and response information was available on 46 treated after 2003, during the era of new agents for plasma cell diseases. In this cohort, there were 5 treatment groups: high-dose melphalan/stem cell transplant (HDM/SCT); bortezomib-based regimens; standard doses of the alkylating agents melphalan or cyclophosphamide; immunomodulatory agents (IMiDs); and rituximab-based regimens. Treatment regimens were assigned by bone marrow pathology and patient-specific factors.

Results: For the 106 patients, the median age at diagnosis was 67 years (range: 38-89 years) with 52 (56%) males. The kidney was the most commonly involved organ (51%) followed by heart (41%) and GI tract (23%). Median IgM was 590 g/dL (range: 29-9130). The clonal population had lambda light chain restriction in 69% of patients. For the 46 patients treated after 2003, overall response rates and rates of very good partial or complete responses were were 100% and 80% respectively, with HDM/SCT; 82% and 30% with bortezomib-containing regimens; 80% and 25% with regimens that included rituximab; 75% and 0% with regimens in which an IMiD was included; and 63% and 20% with other alkylator regimens. There was no association between treatment response and organ involvement, sex, or age.