Tabelecleucel Proves Effective For Patients with R/R EBV+ PTLD

In the ALLELE trial, patients (pts) received tabelecleucel at 2×10⁶ cells/kg doses on days 1, 8, and 15 in 35-day cycles. The response is assessed using independent oncologic response adjudication (IORA) based on the Lugano Classification with LYRIC modification, including clinical and radiographic evaluation (primary assessment). The efficacy objectives included overall response rate (ORR), duration of response (DOR), time to response (TTR), and overall survival (OS), with pts monitored for up to 5 years post-treatment. These analyses included additional pts and longer follow-up compared to previously reported ALLELE data.

Up to November 2021, the analysis included 43 pts (14 HCT, 29 SOT) who received at least one dose of tabelecleucel. The median age was 48.5 years (3.2–81.5), and the most prevalent PTLD subtype was diffuse large B-cell lymphoma (67.4%). At screening, 76.7% of pts had extranodal disease. Among pts aged ≥16 years, 27.5% had an Eastern Cooperative Oncology Group (ECOG) score ≥2, with 42.5% classified as high risk and 47.5% as intermediate risk based on the PTLD adapted prognostic index. The median number of previous systemic treatments was 1 (1–5). Univariate analyses showed consistent efficacy across various baseline characteristics (extranodal disease, ECOG, and number of prior therapies). Patients received a median of 2 cycles (range, 1–6) of tabelecleucel.

In line with previously presented ALLELE data, the overall ORR was 51.2% (22/43, 95% CI: 35.5, 66.7), with HCT pts achieving a 50.0% ORR (7/14, 95% CI: 23.0, 77.0) and SOT pts achieving a 51.7% ORR (15/29, 95% CI: 32.5, 70.6). The best overall response included complete response (CR) in 6 HCT and 6 SOT pts and partial response (PR) in 1 HCT and 9 SOT pts. The median TTR was 1.0 month (0.7–4.7). Among responders, 12 out of 22 had a DOR exceeding 6 months, with a median DOR of 23.0 months (95% CI: 6.8, not estimable).

The overall median OS was 18.4 months (95% CI: 6.9, not estimable), not estimable in HCT (95% CI: 5.7, not estimable), and 16.4 months in SOT (95% CI: 5.0, not estimable). Responding pts demonstrated a higher one-year OS rate (84.4%; 95% CI: 58.9, 94.7) than non-responders (34.8%; 95% CI: 14.6, 56.1).

Serious treatment-emergent adverse events (TEAEs) were reported in 57.1% and 51.7% of HCT and SOT pts, respectively, with fatal TEAEs occurring in 7.1% of HCT and 13.8% of SOT pts. There were no treatment-related fatal TEAEs, graft-versus-host disease (GVHD), organ rejections, or adverse events related to TFR, infusion reactions, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, marrow rejection, or transmission of infectious diseases.

Updated Phase 3 ALLELE data, featuring more pts and longer follow-up, confirmed the consistent and clinically significant benefits of tabelecleucel, including improved overall response rates, extended duration of response, and prolonged overall survival. Notably, no safety concerns were observed, differentiating tabelecleucel as a potential transformative advance in treating relapsed/refractory EBV+ PTLD pts.

Source: https://ebmt2023.abstractserver.com/program/#/details/presentations/1647

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

Choquet, S., Mahadeo, K.M., Baiocchi, R., Beitinjaneh, A., Chaganti, S., Dierickx, D., Dinavahi, R., Gamelin, L., Ghobadi, A., Guzman-Becerra, N., Joshi, M., Mehta, A., Nikiforow, S., Reshef, R., Prockop, S. Paed3-02 UPDATED RESULTS FROM PHASE 3 STUDY TABELECLEUCEL FOR POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL OR SOLID ORGAN TRANSPLANT AFTER FAILURE RITUXIMAB(R) OR R+CHEMOTHERAPY (ALLELE).