A Case Series of B-Cell Lymphoma Becoming CD20-Negative Upon Progression: Tissue is Always an Issue
Introduction/Background/Significance: Loss of CD20 expression in B-cell lymphoma is rare but clinically significant, often leading to disease progression and resistance to anti-CD20 based therapies including monoclonal antibodies and bispecific therapies. This phenomenon poses diagnostic challenges and necessitates alternative treatment approaches. We present a series of three cases in which initially CD20-positive B-cell lymphomas relapsed as CD20-negative disease.
Materials and Methods/Case Presentation/Objective: In the first case, a patient with CD20-positive follicular lymphoma was treated with bendamustine and rituximab and rituximab maintenance. Upon progression, repeat biopsy showed transformation to diffuse large B-cell lymphoma (DLBCL) with negative CD20 expression. In the second case, a patient with refractory CD20-positive follicular lymphoma underwent 5 lines of anti-CD20 monoclonal antibodies-based therapies including rituximab and obinutuzumab, bispecific therapy monsunetuzumab, and CAR-T therapy tisagenlecleucel; but relapse occurred with a biopsy confirming loss of CD20 expression. In the third case, a patient with CD20-positive lymphoma relapsed multiple times. After four lines of rituximab-based treatments and fifth line with epcoritamab, the subsequent biopsy showed CD20-negative DLBCL. In all three cases, initial CD20 expression was lost upon relapse following anti-CD20 based treatments, emphasizing the evolving phenotype of B-cell lymphomas under therapeutic pressure. The loss of CD20 necessitated alternative strategies, including non-CD20 targeted agents and cellular therapies.
Conclusions: These cases highlight the clinical and therapeutic implications of CD20 loss in B-cell lymphomas. They underscore the importance of repeating biopsy at relapse before implementing CD20-directed therapy, which is particularly relevant given the widespread use of anti-CD20 monoclonal antibodies along with the emerging CD20-targeted bispecific antibodies. Awareness of this phenomenon is crucial for optimizing management strategies and improving patients’ outcomes. As the saying goes, "Tissue is always an issue in oncology".
