Complete loss of lineage defining antigens in two cases of B-cell malignancies following CAR-T therapy

Targeted immunotherapy is a promising approach in treating high-risk and refractory/relapsed lymphoid malignancies. Although this strategy has shown a significant success in treating non-Hodgkin B-cell lymphomas and plasma cell myeloma, relapse with loss of targeted antigen can occur. Rarely, complete loss of multiple lineage specific markers can happen. We are describing 2 cases of B-cell neoplasms along with contributing immunohistochemistry, cytogenetic, and molecular results. Post-targeted CAR-T therapy, both cases, one aggressive B-cell lymphoma and the other plasma cell myeloma, lost B-cell, and plasma cell antigens, respectively. Complete loss of lineage specific markers post-targeted therapy is a rare event that makes the diagnosis of the relapsed neoplasm challenging. In this article, we also reviewed the literature and highlighted possible mechanisms of antigen loss following targeted therapy.