Overall Survival By Best Overall Response with Tabelecleucel in Patients with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease Following Solid Organ or Allogeneic Hematopoietic Cell Transplant

Introduction: Tabelecleucel is an investigational, off-the-shelf, allogeneic Epstein–Barr virus (EBV)-specific T-cell immunotherapy being studied in patients (pts) with serious EBV-driven diseases, including post-transplant lymphoproliferative disease (EBV⁺ PTLD). Initial management of EBV⁺ PTLD following solid organ transplant (SOT) and allogenic hematopoietic cell transplant (HCT) may include reduction in immunosuppression and/or off-label rituximab ± chemotherapy (CT). In pts with EBV⁺ PTLD following HCT, median overall survival (OS) was ~1.7 months after failure of rituximab (Socié EBMT 2020) and ~3 months following SOT in pts who relapsed with rituximab and who did not respond to or did not receive CT (Zimmerman EHA 2019). We have previously shown that pts with EBV⁺ PTLD who responded to tabelecleucel had clinical benefit, including >80% estimated 2-year survival rates (Prockop JCI 2020, Prockop EBMT 2021, Prockop ATC 2021). Here, we report aggregate OS across pts with EBV⁺ PTLD following HCT and SOT (combined population) by best overall response (BOR; eg, CR or PR) with tabelecleucel treatment.

Methods: Treatment response and OS were assessed in three open-label studies (NCT00002663, NCT01498484 and NCT02822495). Analyses based on pooled data from the three studies were performed. All pts received tabelecleucel at ~2 x 10⁶ cells/kg on Days 1, 8 and 15 in 35-day treatment cycles. Pts who did not initially respond could switch to tabelecleucel with a different human leukocyte antigen (HLA) restriction (restriction switch), and were treated until unacceptable toxicity, maximal response, or up to four different HLA restrictions. The length of post-treatment follow-up (if any) varied per protocol.

Results: In this combined analysis, 76 pts with EBV⁺ PTLD relapsed or refractory to rituximab (HCT; n=50) or rituximab ± CT (SOT; n=26) were treated with a median (range) of 2 (1–9) cycles of tabelecleucel. The investigator-assessed objective response rate, defined as the proportion of pts with BOR of CR or PR, was 63.2% overall (48/76), including 32 pts with CR and 16 pts with PR (Table 1, Figure 1). The median OS (95% confidence interval [CI]) for all treated pts was 54.6 months (14.8, 115.0) after a median follow-up (range) of 14.8 (0.4–115.0) months. The estimated overall 1- and 2-year OS rates (95% CI) were 65.8% (53.6, 75.5) and 57.8% (45.4, 68.5), respectively. The estimated 1- and 2-year OS rates (95% CI) in responders (CR+PR, n=48) were 91.3% (78.4, 96.6) and 86.2% (71.7, 93.6), respectively. Two-year estimated OS rates (95% CI) were 86.2% (67.0, 94.6) and 86.5% (55.8, 96.5) for pts with CR and PR, respectively (Table 1). Treatment was well tolerated with no confirmed evidence for graft vs host disease, cytokine release syndrome, SOT rejection, or neurologic events attributable to tabelecleucel in these very sick, treatment refractory, and immunocompromised pts.

Conclusions: Tabelecleucel was well tolerated. Additionally, the combined data reported here show that pts whose EBV⁺ PTLD failed to respond to rituximab (HCT) or rituximab ± CT (SOT) and who responded to tabelecleucel experienced long-term survival. Importantly, pts who achieved a PR with tabelecleucel derived similar OS benefit to those who achieved a CR. These results are consistent with those reported previously in separate subsets of pts with EBV⁺ PTLD following HCT (Prockop EBMT 2021) or SOT (Prockop ATC 2021).