Session: 622. Lymphomas: Translational – Non-Genetic: Poster II
Methods: Tumor and blood samples were collected before tafasitamab treatment (baseline) and at end of treatment (EOT) from anti-CD19–naive patients. Tumor CD19 expression was assessed using immunohistochemistry (IHC) assays with a validated mAb that binds to an intracellular epitope of CD19 clone LE-CD19 (Volgina A, et al. EHA 2024). In addition, next-generation sequencing (NGS) was performed with DNA extracted from patient samples.
Results: As of the June 30, 2024, data cutoff, EOT samples from a total of 29 patients with R/R DLBCL were analyzed by IHC following tafasitamab treatment (L-MIND, n=6; firmMIND, n=6; real world, n=17). All samples were CD19+ at EOT, except 1 that was also negative at baseline. The length of time between last tafasitamab dose and EOT biopsy collection ranged from 1 to 200 days. These samples showed ≥60% of tumor cells staining CD19 positive, with an intensity score of 1-3+ by IHC. NGS was performed on 6 EOT biopsies (L-MIND) and 8 peripheral blood samples from patients who were positive for minimal residual disease at EOT (topMIND). Sequencing revealed no likely somatic mutations in the CD19 gene.
Preclinical analysis in the SU-DHL4 lymphoma cell line suggests that CD19 is internalized upon tafasitamab binding and this complex is trafficked into the lysosomes. However, some CD19 is retained on the cell surface and CD19 returns to the baseline level within 24 hours after removing tafasitamab from culture.
Conclusions: The results of this study of EOT tumor and blood samples collected from patients treated with tafasitamab in clinical trials or in the real world demonstrate that the CD19 antigen is retained on tumor cells and no somatic mutations in the CD19 gene are observed following tafasitamab therapy. These results suggest the potential to treat patients who received tafasitamab with subsequent CD19-targeting agents, such as CAR-T therapy. In addition, these findings support the adoption of the LE-CD19 clone as the standard antibody for assessing CD19 expression in clinical practice. Analyses with larger sample sizes are ongoing to confirm these findings.
Disclosures: Duell: Incyte: Consultancy, Research Funding; Novartis: Honoraria; Gilead-Kite: Honoraria; BMS: Honoraria; Janssen: Honoraria; Beigene: Consultancy; Abbvie: Consultancy. Alvarez Arias: Incyte: Current Employment, Current equity holder in publicly-traded company. Volgina: Incyte: Current Employment, Current equity holder in publicly-traded company. Rumberger: Incyte: Current Employment, Current equity holder in publicly-traded company. Larsen: Genentech: Research Funding; Kite/Gilead: Consultancy; Roche: Consultancy. Rosenwald: MorphoSys: Other: institutional research contract; Incyte: Other: Institutional research contract .
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