Abstract 1051P
Background
Patients (pts) with PID or AID are at higher risk of developing Epstein-Barr virus-driven lymphoproliferative disease (EBV+ LPD). Although there are no approved therapies, initial treatment (tx) of EBV+ PID or AID LPDs includes chemo +/- rituximab; however, effective options after tx failure are limited. Tabelecleucel (tab-cel), an investigational off-the-shelf, allogeneic EBV-specific T-cell immunotherapy, has previously shown clinical activity in pts with EBV+ post-transplant lymphoproliferative disease (Prockop S et al. JCI 2020; EHA 2018). Here, we report data in pts with EBV+ PID and AID LPDs treated with tab-cel, after failure of initial therapies, in an expanded access programme (NCT02822495).
Methods
Pts received tab-cel at 1.6–2.0 x 106 cells/kg/dose on Days 1, 8 and 15, with investigator-assessed response per Lugano criteria on Day 28 of each 5-week cycle. Pts who do not respond (progressive disease [PD] or stable disease [SD]) can switch to tab-cel with a different human leukocyte antigen (HLA) restriction (restriction switch). Pts continued tx until unacceptable toxicity, maximal response (2 consecutive complete responses [CR] or 3 partial responses [PR]), or up to 4 different HLA restrictions. All tx-emergent serious adverse events (TESAEs) were collected.
Results
Pt characteristics, treatment exposure, responses and safety data are reported in the table. Objective response rates (ORR) were 37.5% in the PID (3/8) and 33.3% in the AID (3/9) LPD cohorts. There were 5 pts with tx-related TESAEs in the PID (n=3) and AID LPD (n=2) cohorts. No fatal events were reported as tx-related.
Conclusions
Tab-cel was well tolerated and showed evidence of clinical activity in pts with EBV+ AID and PID LPDs. Based on these results, further clinical investigation of tab-cel in EBV+ PID and AID LPDs is planned within an upcoming study (ATA129-EBV-205). Table: 1051P
| EBV+ PID LPD (N=8) | EBV+ AID LPD (N=9) | |
| Median age, yrs (range) | 25.0 (1–91) | 64.0 (34–69) |
| Sex (M) – n (%) | 4 (50.0) | 7 (77.8) |
| Median no. of tabelecleucel tx cycles (range) | 2.0 (1–3) | 2.0 (1–4) |
| Best overall response – n (%) | ||
| Responders (CR + PR) | 3 (37.5) | 3 (33.3) |
| CR | 1 (12.5) | 1 (11.1) |
| PR | 2 (25.0) | 2 (22.2) |
| SD | 2 (25.0) | 0 (0.0) |
| PD | 3 (37.5) | 6 (66.7) |
| Pts with tx-related TESAEs* – n (%) | 3 (37.5) | 2 (22.2) |
*Depressed level of consciousness (grade 2, led to tx discontinuation), hypoxia (grade 3), pyrexia (grade 1), skin ulcer and tumour flare (both grade 3, same pt), graft versus host disease (GvHD) in skin (grade 1, pt with ongoing chronic skin condition; no biopsy performed to confirm GvHD). Data as of 28 Jan 2020.
Clinical trial identification
NCT02822495.
Editorial acknowledgement
Anna Sanniti, PhD from Seques (AMICULUM Ltd).
Legal entity responsible for the study
Atara Biotherapeutics.
Funding
Atara Biotherapeutics.
Disclosure
S. Nikiforow: Advisory/Consultancy, Travel/Accommodation/Expenses: Kite; Advisory/Consultancy, Travel/Accommodation/Expenses: Gilead; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Nkarta. R. Baiocchi: Honoraria (self), Advisory/Consultancy, Leadership role, Research grant/Funding (self): Prelude Tx; Honoraria (self), Advisory/Consultancy, Leadership role, Research grant/Funding (self): Viracta; Honoraria (self): Upstate Medical Center; Advisory/Consultancy: Atara; Licensing/Royalties: Ohio State University; Travel/Accommodation/Expenses: AIDS Malignancy Consortium (NIH/NCI); Travel/Accommodation/Expenses: Lymphoma Research. S. Nasta: Advisory/Consultancy: Merck; Research grant/Funding (self): Genentech/Roche; Research grant/Funding (self): Millenium/Takeda; Research grant/Funding (self): Rafael; Research grant/Funding (self): Debiopharm; Research grant/Funding (self): Pharmacyclics. K.M. Mahadeo: Research grant/Funding (self), Principal Investigator: Atara. J. Whangbo: Advisory/Consultancy, Travel/Accommodation/Expenses: Orchard Therapeutics. P. Phuong, W. Navarro, L. Gamelin, Y. Sun, N. Guzman-Becerra: Shareholder/Stockholder/Stock options, Full/Part-time employment: Atara Biotherapeutics. S. Prockop: Research grant/Funding (self), Through MSK: Atara. All other authors have declared no conflicts of interest.