Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: EBV+ PTLD is often a fatal disease. Tab-cel is an investigational off-the-shelf, allogeneic T-cell immunotherapy specific for EBV antigens. Functional in vivo expansion approximated by a limiting dilution analysis of EBV-CTLp has previously been correlated to clinical response.
*Methods: We conducted analyses of reported peak circulating EBV-CTLp levels following tab-cel administration in correlation to response and safety across two studies (NCT00002663, NCT01498484) in rituximab refractory or relapsing EBV+ PTLD following HCT or SOT (N=42).
*Results: Two cohorts were defined by the lowest EBV-CTLp quartile (n = 11) and the combined upper 3 quartiles (n = 31). Twenty-five of 31 subjects (80.6%) in upper quartiles exhibited a clinical response compared to 3 of 11 subjects (27.3%) in the lowest quartile. Eighteen of 20 complete responses and 7 of 8 partial responses demonstrated peak CTLp values in the upper quartiles of the population. Overall survival (OS) rate in subjects exhibiting CTLp values in the upper quartiles was 83.9% (95% CI: 65.5-92.9%) at 1 year and 66.1% (95% CI: 45.9-80.2%) at 2 years, compared to 18.2% (95% CI: 2.9-44.2%) in the lowest quartile over the same periods. OS is commensurate with a hazard ratio of 0.168 in favor of subjects with higher EBV-CTLp (95% CI: 0.067-0.425; Log-Rank Test p-value < 0.001). Subjects demonstrating clinical responses experienced median CTLp values of 36.2 CTLp/ml (15.6-155 interquartile range), whereas non-responders exhibited significantly lower (p = 0.001, based on Wilcoxon Rank Sum test) median CTLp of 0.07/ml (0.01-5.5 interquartile range). Tab-cel was well tolerated across both studies, with a safety profile in each group consistent with the underlying clinical condition of patients.
*Conclusions: These analyses illustrate the correlation of peak EBV-CTLp to clinical benefit in subjects receiving tab-cel. Significant correlation of EBV-CTLp with ORR and OS are consistent with potential use as a functional biomarker for the expansion of EBV-specific T-cells in the treatment of EBV+ PTLD in the rituximab refractory/relapsing setting.
To cite this abstract in AMA style:Shen R, Guzman-Becerra N, Sun Y, Forozan F, Prockop S, Doubrovina E, O'Reilly R, Li X, Hiremath M, Gamelin L, Navarro W, Aftab B. Epstein-Barr Virus-Specific Cytotoxic T Lymphocyte Precursors (EBV-CTLp) after Tab-cel Correlates with Response & Survival in Rituximab Relapsing or Refractory Ebv+ Posttransplant Lymphoproliferative Disease (PTLD) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/epstein-barr-virus-specific-cytotoxic-t-lymphocyte-precursors-ebv-ctlp-after-tab-cel-correlates-with-response-survival-in-rituximab-relapsing-or-refractory-ebv-posttransplant-lymphoproliferative/. Accessed October 27, 2020.
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