Clinical Presentation and Treatment Responses In IgM-Related AL Amyloidosis

AL amyloidosis is a multiorgan disease due to deposition of misfolded monoclonal immunoglobulin light chains. AL amyloidosis associated with IgM paraproteinemia is a rare variant of this disease, constituting approximately 6% of AL amyloidosis cases in the literature. The clonal cell of origin may be a plasma cell or a lymphoplasmacytic cell, and treatments targeting each of these populations have been employed. This study defines the clinical and laboratory characteristics of IgM-related AL amyloidosis patients as well as their response to different therapeutic regimens.

We identified 94 patients with IgM-related AL amyloidosis evaluated at the BUMC Amyloidosis Center from 2003 through 2012 for which data was available on 50 who completed treatment. The median age at diagnosis was 65 years (range: 42-79 years) with 31 (62 %) males. The most commonly involved organ was the kidney (59%) followed by heart (37%) and GI tract (22%). The mean IgM was 1049 g/dL (range: 29-9130). The clonal population had lambda light chain restriction in 34 (68%) of patients. Patients were categorized into 5 treatment groups: high-dose melphalan/stem cell transplant (HDM/SCT), bortezomib-based, non-transplant alkylating agents based (melphalan or cyclophosphamide), immunomodulatory agents (IMiDs), and rituximab-based. This grouping was not mutually exclusive. The highest hematologic response rate was observed with HDM/SCT (10/10: 100%), followed by non-transplant alkylating agents (16/22: 73%), bortezomib (7/10: 70%) rituximab (9/13: 69%) then by IMiDs (2/4: 50%). We did not observe an association between positive response to treatment and organ involvement, sex or age at diagnosis.

In conclusion, IgM-related ALamyloidosis is an unusual variant of AL amyloidosis. Multiple active therapies with different mechanisms of action exist; treatment should be tailored based upon clinicopathologic and patient-specific factors.