Tabelecleucel for EBV-Driven Post-transplant Lymphoproliferative Disease

Patients (pts) with EBV-driven post-transplant lymphoproliferative disorder (EBV+ PTLD) are being studied using tabelecleucel, an off-the-shelf, allogeneic T-cell immunotherapy that targets the Epstein-Barr Virus (EBV). There is an urgent need for therapies in this ultra-rare disease, as the median overall survival (OS) after rituximab (R) chemotherapy (C) failure is 0.7 months in EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT) (Sanz ASH 2021) and 4.1 months following solid organ transplant (SOT) (Dharnidharka ASH 2021). Promising results have been shown with tabelecleucel (Prockop JCI 2020). Patients with relapsed/refractory (R/R) EBV+ PTLD who responded to tabelecleucel had an objective response rate (ORR) of >60% and >80% 2-year OS (Prockop EBMT 2021, Prockop ATC 2021, Prockop ASH 2021). So far, tumor flare reaction (TFR) is the only known safety concern associated with tabelecleucel treatment for EBV+ PTLD, according to data from more than 180 patients (Atara Biotherapeutics, Data on file). Patients with EBV+ PTLD following HCT and R failure (n=33) or SOT and RC failure (n=33) are eligible to participate in ALLELE, a multicenter, open-label trial examining tabelecleucel.

Patients (Pts) get 2 x 106 cells/kg of tabelecleucel on Days 1, 8, and 15 of 35-day cycles. The LYRIC variant of the Lugano Classification is used for the primary evaluation with the investigator’s assessment to determine the level of response. Time to response, OS, DOR, and TTR are all efficacy measures. Patients are monitored for up to 5 years after treatment to determine their prognosis. There were 38 pts (14 HCT, 24 SOT) who could be assessed by IORA and had at least 6 months of follow-up as of May 2021. Patients had a median age of 52 (range: 3.2-81.5 years), a median number of prior lines of systemic treatment of 1 (range: 1-5), and 44.4%/47.2% were classified as high/intermediate risk according to the PTLD-adapted prognostic criteria. The most common number of tabelecleucel cycles given to patients with R/R HCT and SOT was three cycles (one to five). Overall ORR was 50.0% (19/38, 95% CI: 33.4, 66.6), HCT ORR was 50.0% (7/14, 95% CI: 23.0, 77.0), and SOT ORR was 50.0% (12/24, 95% CI: 29.1, 70.9). Eleven of the nineteen respondents had a DOR greater than six months, while the median DOR was not attained. The median TTR was 1.1 (0.7-4.7) months.

The overall median overall survival (OS) was 18.4 months (95% CI: 6.9, NR), with the upper limit not yet reached (NR), while the OS for hematopoietic cell transplantation (HCT) was also not yet reached, and for solid organ transplantation (SOT) it was 16.4 months (95% CI: 3.5, NR). The 1-year survival rates were 61.1% (95% CI: 42.9, 75.0) for the overall population, 66.8% (95% CI: 32.4, 86.6) for HCT, and 57.4% (95% CI: 35.2, 74.5) for SOT. Among responders, the median OS was not reached (NR) (95% CI: 16.4, NR), while for non-responders, it was 5.7 months (95% CI: 1.8, 12.1). Responders demonstrated a higher 1-year survival rate compared to non-responders: 89.2% (95% CI: 63.1, 97.2) versus 32.4% (95% CI: 12.1, 54.9)

There were no treatment-related TEAE deaths. No graft-versus-host disease or organ rejection cases were documented, and no cases of transfusion response, infusion reaction, cytokine release syndrome, marrow rejection, or transfer of infectious illnesses were observed. In a patient population with low survival and no licensed medications, tabelecleucel Phase 3 data revealed clinically important benefits, including promising ORR and OS. The tolerability of tabelecleucel was high, with no signs of the side effects common to previous adoptive T-cell treatments.

Source:https://library.ehaweb.org/eha/2022/eha2022-congress/357120/susan.prockop.tabelecleucel.for.ebv-driven.post-transplant.lymphoproliferative.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26864%2Amarker%3D1751%2Afeatured%3D17676

Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03394365

Susan Prockop, Amer Beitinjaneh, Sylvain Choquet, Saurabh Dahiya, Rajani Dinavahi, Rafic Farah, Laurence Gamelin, Armin Ghobadi, Aditi Mehta, Pratima Nayak, Ran Reshef, Gowri Satyanarayana, Patrick Stiff, Wei Ye, Kris Michael Mahadeo, MPH/TABELECLEUCEL FOR EBV-DRIVEN POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL OR SOLID ORGAN TRANSPLANT AFTER FAILURE OF RITUXIMAB ± CHEMOTHERAPY (ALLELE) Retrieved May 4, 2023, from library.ehaweb.org website: https://library.ehaweb.org/eha/2022/eha2022-congress/357120/susan.prockop.tabelecleucel.for.ebv-driven.post-transplant.lymphoproliferative.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26864%2Amarker%3D1751%2Afeatured%3D17676