PII-053 - EVALUATION OF IMPACT OF PRIOR CAR T THERAPY ON PHARMACOKINETICS (PK) AND PHARMACODYNAMICS (PD) OF ODRONEXTAMAB, A CD20×CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL).

M. Zhu, X. Meng, J. Brouwer-Visser, H. Yan, D. Conrado, M. Bravo Padros, L. Harnisch, A. Chaudhry, H. Mohamed, S. Ambati, J. Davis, X. Xu; Regeneron Pharmaceuticals, Inc..

Background: Odronextamab binds CD20 on B cells and CD3 on T cells, resulting in T-cell-mediated cytotoxicity of targeted B cells. Its clinically meaningful efficacy in R/R DLBCL was observed independent of prior chimeric antigen receptor T cell therapy (CAR T). This analysis evaluated the effects of prior CAR T on the kinetics and reconstitution of immune cells, and on clinical response to odronextamab. PK and PD of odronextamab were assessed in CAR T naïve (ELM-2, NCT03888105) or post CAR T (ELM-1, NCT02290951) patients (pts).

Methods: PK, PD (T and B cell counts, cytokine profiles, and IgG levels), and response to intravenous odronextamab at doses of 160 mg weekly then 320 mg every 2 weeks were evaluated in pts with DLBCL who were either CAR T naïve (n=113) or relapsed/refractory to prior CAR T (n=44). The baseline immune profile in the post CAR T group was assessed prior to the 1st odronextamab dose and compared with the baseline immune profile in the CAR T naïve group.

Results: PK of odronextamab were similar in the post CAR T and CAR T naïve groups. Approximately 50% of pts had measurable B cells at baseline in both DLBCL groups; median baseline B cell counts were 18 cells/µL and 0.18 cells/µL in the CAR T naïve and post CAR T groups, respectively, indicating that B cell recovery was slow post CAR T. Baseline T cell counts were higher in the CAR T naïve group than in the post CAR T group; T cell expansion was similar in the two groups but higher in odronextamab responders than nonresponders. Pts post CAR T had generally lower lymphocytes and IgG levels before receiving odronextamab than CAR T naïve pts, indicating that reconstitution of immune cells was still under way. Cytokine profiles were similar in the two groups. In the post CAR T group, the median time to receipt of the 1st odronextamab dose post CAR T was 8 and 6 months in odronextamab responders and nonresponders, respectively. Most nonresponders received odronextamab 2–5 months post CAR T, with lack of response potentially due to highly aggressive disease, lack of sufficient recovery time for immune cells, or both.

Conclusion: These data suggest that prior CAR T treatment may affect B cell and T cell recovery, but have less effect on T cell expansion following odronextamab treatment. This analysis adds to our understanding of immune cell reconstitution post CAR T and its potential effect on odronextamab treatment.