CD19 expression is preserved following CD19-directed monoclonal antibody therapy with tafasitamab

Introduction The potential risk of eliminating or reducing CD19 expression following CD19-targeted therapies has raised questions about the optimal treatment sequencing strategies for B-cell malignancies. This study assessed CD19 expression and mutational status in samples from patients with relapsed or refractory B-cell malignancies who received tafasitamab, an anti-CD19 monoclonal antibody. Methods Biopsy and peripheral blood samples were collected from a total of 100 patients with relapsed or refractory B-cell malignancies who received tafasitamab in a clinical trial or a real-world setting. Post-treatment samples collected from 66 patients were available for assessment of CD19 protein expression; six samples were excluded from the analyses as CD19 expression could not be assessed due to lack of residual lymphoma cells. The remaining 60 samples were assessed by either immunohistochemistry (n=46) or flow cytometry (n=14). Next-generation sequencing (NGS) was used to assess CD19 mutational status (n=39) and transcript expression (n=4). CD19 retention in lymphoma cell lines treated with tafasitamab was assessed by immunohistochemistry and flow cytometry. Results Of 46 patient samples assessed by immunohistochemistry, 45 (98%) were CD19 positive after tafasitamab treatment. CD19 expression was retained in all 14 samples analyzed by flow cytometry. NGS of 39 samples revealed no somatic CD19 mutations. CD19 expression was transiently masked in lymphoma cells treated with tafasitamab when assessed by flow cytometry; however, expression was detectable by immunohistochemistry at all time points assessed. Conclusion These data suggest that tafasitamab treatment, even in the most recent line, may not preclude subsequent treatment with other CD19-targeting agents.