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. 2024 Dec;13(6):268-277.
doi: 10.14740/jh1341. Epub 2024 Dec 2.

Retrospective Study of CD20 Expression Loss in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Joseph P Marshalek  1 , Xin Qing  2 , Marcin Dragan  1 , Sarah Tomassetti  1
Affiliations

Retrospective Study of CD20 Expression Loss in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Joseph P Marshalek et al. J Hematol. 2024 Dec.

Abstract

Background: CD20-targeted therapies are widely used in the management of B-cell lymphomas. Re-treatment with CD20-directed agents is common; however, previous research has demonstrated loss of CD20 expression at relapse in a subset of patients.

Methods: In this single-center retrospective cohort of 243 patients, CD20 analysis was performed by immunohistochemistry (IHC) and/or flow cytometry at diagnosis and at relapse if a biopsy was performed.

Results: Of 109 patients with relapsed or refractory B-cell lymphoma, 59 patients with CD20-positive lymphoma at diagnosis underwent a biopsy at relapse for a total of 76 biopsies across all relapses. The rate of partial or complete CD20 expression loss was 11.9% (four patients with partial loss, three patients with complete loss). There were four cases of CD20 loss at first relapse (three IHC, one flow cytometry), two at second relapse (one IHC, one IHC and flow cytometry), and one at fifth relapse (IHC and flow cytometry). CD20 antigen escape was observed in marginal zone lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL). All patients with CD20 expression loss previously received rituximab. Among patients with CD20 antigen escape, 85.7% had stage IV disease, and median overall survival after CD20 loss was 4 months. In the group of five patients with indolent lymphoma and CD20 expression loss, three patients (60%) had concurrent transformation to high-grade lymphoma.

Conclusions: This study, which reinforces the importance of repeating a biopsy at relapse before implementing CD20-directed therapy, is particularly relevant given the widespread use of rituximab along with the emerging significance of CD20-targeted bispecific antibodies in the management of B-cell lymphomas.

Keywords: Antigen escape; CD20; Lymphoma; Rituximab.

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Conflict of interest statement

The authors have no relevant conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flow diagram of patient eligibility.
Figure 2
Figure 2
Rate of CD20 expression loss at relapse by lymphoma type.
Figure 3
Figure 3
Immunohistochemistry images for a marginal zone lymphoma with complete CD20 loss showing (a) CD20 expression at diagnosis, (b) CD20 negativity at second relapse, (c) PAX5 positivity, thereby confirming B-cell lineage, at second relapse.
Figure 4
Figure 4
Immunohistochemistry image for a diffuse large B-cell lymphoma with partial weak CD20 expression at first relapse, representing partial CD20 loss. A subset of large lymphoma cells are weakly positive for CD20 (wide arrow), while the background small B cells are strongly positive for CD20 (thin arrow).
See this image and copyright information in PMC

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