CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy

TL;DR

This study explores how CS1 expression in NK cells and plasma cells affects elotuzumab therapy and CAR-T efficacy in plasma cell dyscrasias.

Contribution

The study reveals that elotuzumab enhances NK cell cytotoxicity against tumors regardless of CS1 expression levels.

Findings

MM patients have higher CS1 expression in plasma cells compared to other PCD patients.

CS1 expression in plasma cells correlates strongly with that in NK cells.

Elotuzumab boosts NK cell cytotoxicity against tumor cells independent of CS1 levels.

Abstract

Treatment with elotuzumab alone has no discernible antitumor effect and progress in chimeric antigen receptor T cells (CAR-T) therapy targeting CS1 is relatively slow. A retrospective analysis was performed on 236 patients with multiple myeloma (MM) and 30 patients with other plasma cell dyscrasias (PCDs). CS1 expression in NK cells, lymphocytes, and monoclonal plasma cells was assessed using multiparameter flow cytometry. Furthermore, new explorations were undertaken regarding the antitumor applications of elotuzumab. Patients with MM had significantly higher CS1 expression levels in plasma cells than other patients with PCDs, with no significant differences between lymphocytes and NK cells. In both patients with MM and other PCDs, CS1 expression was significantly higher in plasma cells than in NK cells and lymphocytes. Univariate and multivariate analyses revealed a significant correlation between CS1 expression in plasma (r = 0.60; P < 0.001) and NK (r = 0.79; P < 0.001) cells. Factors such as cytogenetic abnormalities, disease progression, and survival were not associated with CS1 expression in NK cells. Moreover, this study showed that elotuzumab strongly increases the cytotoxicity of NK cells against non-plasma and plasma tumor cells independent of their CS1 expression level. This underscores the potential of elotuzumab in combination with NK cells as an effective therapeutic strategy against a broad spectrum of tumor types.

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