Collectively, these results establish CD70 as a promising therapeutic target for high-risk multiple myeloma, particularly for patients who relapse after BCMA-directed therapy, providing preclinical support for the ongoing phase I/II clinical trial of CD70-targeting CAR NK cells (NCT05092451).<h4>Significance</h4>We demonstrate that CD70 expression is elevated in patients with high-risk multiple myeloma and in patients with t(4;14) translocation. This evidence concerns the gene CD70 and plasma cell myeloma.