Expression of Kappa Myeloma Antigen (KMA) and Lambda Myeloma Antigen (LMA) on Malignant but Not Normal Plasma Cells Offers Novel Therapeutic Targets for Patients With Myeloma, Amyloidosis and Other Plasma Cell Dyscrasias.

Background: Kappa myeloma antigen (KMA) and lambda myeloma antigen (LMA) are antigens expressed on the surface of malignant plasma cells (PCs) that may have potential as immunotherapy targets. They arise from conformational epitopes in the constant regions of lipid-associated light chains and are not found on PCs in normal bone marrow (BM).

Materials and methods: Antibodies to KMA and LMA (KappaMab, LambdaMab) and other antigens were used to compare the expression of KMA, LMA, B cell maturation antigen (BCMA), CD56 and SLAMF7 on bone marrow PCs. QuantiBrite beads were used to calculate antigen densities. LMA expression was evaluated in a panel of normal human and plasmacytoma tissues.

Results: Bone marrow aspirates (n = 195) were analyzed from patients with various clonal plasma cell dyscrasias (PCDs) (114 MM, 39 MGUS, 13 plasmacytoma, 9 SMM and 20 AL-amyloidosis). SLAMF7 expression was universal. KMA was present on 87 of 121 (72%) and LMA on 56 of 74 (76%) samples. BCMA expression exceeded KMA and LMA except in AL-amyloidosis, where KMA and LMA were expressed in 18 of 20 cases, including 4 in which LMA was expressed without BCMA. When all PCDs were considered, antigen density of KMA and LMA exceeded that of BCMA. LMA expression was restricted to malignant PCs and occasional mononuclear cells in normal mucosal associated lymphoid tissue.

Conclusions: The broad and selective expression of KMA and LMA on malignant PCs and the high antigen density highlight the potential of these as valuable targets for immunotherapies in a variety of PCDs including AL-amyloidosis.