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    Myeloma Novel Drug Targets and agents

    Category: Myeloma Novel Drug Targets and agents

    Novel therapeutic targets kappa myeloma antigen (KMA) and lambda myeloma antigen (LMA) are expressed on malignant plasma cells from patients with plasma cell dyscrasias but not on normal plasma cells

    (PA-313) Novel Therapeutic Targets Kappa Myeloma Antigen (KMA) and Lambda Myeloma Antigen (LMA) Are Expressed on Malignant Plasma Cells from Patients with Plasma Cell Dyscrasias but Not on Normal Plasma Cells

    Thursday, September 18, 2025
    Introduction: Kappa myeloma antigen (KMA) and lambda myeloma antigen (LMA) are lipid-associated antigens arising from conformational epitopes in the constant regions of light chains  expressed on the surface of malignant plasma cells (PCs). They are not found on normal PCs. Therapeutic monoclonal antibodies have been developed to recognize KMA and LMA. Their expression on a broad range of plasma cell dyscrasias (PCDs) and normal tissues has not been fully documented.

    Methods: Antibodies to KMA and LMA (KappaMab and LambdaMab) and other antibodies were used to compare the expression of KMA, LMA, B cell maturation antigen (BCMA), CD56 and SLAMF7 on bone marrow PCs from patients with a range of PCDs. QuantiBrite beads were used to calculate antigen densities. LMA expression was evaluated using immunohistochemistry (IHC) on a panel of normal human and plasmacytoma tissues.

    Results:

    Bone marrow aspirates (n=195) were analyzed from patients with various PCDs including 114 cases of multiple myeloma (MM), 39 MGUS, 13 plasmacytoma, 9 smoldering multiple myeloma (SMM) and 20 AL-amyloidosis. KMA was present on 87 of 121 (72%) and LMA on 56 of 74 (76%) samples. KMA and LMA were never co-expressed. Across all types of PCD, KMA and LMA were expressed on PCs in 60-100% of cases. KMA and LMA were universally expressed with CD38 and SLAMF7 but in some cases (n=10) were expressed in the absence of BCMA expression. Antigen density of KMA and LMA was similar to BCMA in cases of myeloma but was significantly greater in non-myeloma PCDs (for KMA 1210 v 1121 molecules PE/cell, p=0.02, for LMA 1436 v 1178 molecules PE/cell, p=0.03). LMA was expressed on plasma cells from 13 of 14 cases of lambda AL-amyloidosis and KMA from 5 of 6 cases of kappa AL-amyloidosis. Longitudinal samples from two patients whose disease progressed from MGUS and SMM to MM demonstrated an increase in LMA expression and higher antigen density compared to BCMA. LMA expression was restricted to malignant PCs and occasional mononuclear cells in normal mucosal associated lymphoid tissue but not on normal bone marrow PCs.

    Conclusions: KMA and LMA were only expressed on clonal but not on normal PCs. Antigen expression was independent of the Ig subtype, the number of bone marrow PCs and the Ig and FLC serum concentrations. In some cases of MM, the frequency and density of antigen expression increased as MM evolved. Density of KMA and LMA was increased over BCMA especially in non-myeloma PCDs. 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.