Tabelecleucel Demonstrates Efficacy, Safety in Phase 3 Trial for EBV-positive Post-transplant Lymphoproliferative Disease

Tabelecleucel (tab-cel), an allogeneic Epstein–Barr virus (EBV)-specific T-cell immunotherapy which has been approved in the European Union, has produced clinically meaningful outcomes and has demonstrated a promising safety profile in patients with EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD) treated in the phase 3 ALLELE clinical trial (NCT03394365). Results were presented at the 2023 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Orlando, Florida, February 15-19, 2023.

The trial treated 43 patients who had EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT), and for whom treatment with rituximab or rituximab and chemotherapy was not effective. Participants received 2x10⁶ cells/kg on days 1, 8, and 15 in 35-day cycles. The included patients had received between 1 and 6 doses (median, 2) as of the November 2021 data cutoff. Among patients who received at least 1 dose of tab-cel, the overall response rate (ORR) was 51.2% (22/43; 95% CI: 35.5-66.7). For the 14 patients who had undergone HCT, the ORR was 50% (7/14; 95% CI: 23.0-77.0) and for the 29 patients who had undergone SOT, the ORR was 51.7% (15/29; 95% CI: 32.5-70.6). The complete response rate was 27.9% across all treated patients, 42.9% for HCT, and 20.7% for SOT. The partial response rate was 23.3% across all patients, 7.1% for HCT, and 31% for SOT. The median overall survival (OS) for the treated patients was estimated to be 18.4 months, and it was noted that patients who responded to tab-cel had an 84.4% OS rate at 1 year, while patients who did not respond to tab-cel had a 34.8% OS rate at 1 year.

“What is remarkable is those responses being durable, with a median duration of response of about 23 months, and they were quick responses...” Amer Beitinjaneh, MD, University of Miami/Jackson Memorial Hospital, said during his presentation of the data. “The median time to response was 1 month, so basically 1 cycle of the treatment.”

In terms of safety, tab-cel was well-tolerated and did not show evidence of safety concerns typical in other adoptive T-cell therapies; there were no cases of tumor flare reaction, transmission of infectious diseases, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immunogenicity events of infusion reactions and marrow rejection. In addition, there were no cases of tab-cel-related graft versus host disease or organ rejection. In total, 53.5% (n=23) of the treated patients experienced serious adverse events (SAEs), and 11.6% (n=5) of patients experienced fatal SAEs. However, only 9.3% (n=4) of patients experienced SAEs deemed related to treatment, and none of these were fatal. It was noted that there was no trend in treatment-related SAEs, with all but pyrexia occurring in single patients only. Two patients experienced treatment-related SAEs that were grade 3 or higher. Beitinjaneh noted that these treatment-related SAEs included cases of hypertension and hypoxia, which both resolved.

The ages of the 43 treated patients ranged from 3.2 to 81.5 years (median, 48.5). The majority of the patients were male (55.8%) and white (83.7%). The Eastern Cooperative Oncology Group (ECOG) score for the patients ranged from 0 to 3 (median, 1), with 27.5% of participants aged 16 years or older having an ECOG score of 2 or greater. Participants had received between 1 and 5 prior lines of systemic treatment (median, 1). Twenty-nine (67.4%) of the participants had diffuse large B-cell lymphoma, 3 (7%) had plasmablastic lymphoma, and 11 (25.6%) had other PTLD morphologies. Seventeen patients had high-risk disease, 19 had intermediate risk, 3 had low risk, and 1 had an unknown risk level. Extranodal disease was observed in 33 patients at screening.

“[When initial therapies for PTLD are not effective], outcomes are dismal, with an estimated median overall survival of 0.7 months for HCT-PTLD and a median overall survival of about 4 months for SOT-PTLD once the initial treatment with rituximab-based treatments fails,” Beitinjaneh stated. “So there is a great need for a new therapy for those unfortunate patients.” He concluded the presentation by stating that tab-cel, based on the results reported, could represent a potentially transformative treatment for this patient population.

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REFERENCE

Beitinjaneh A, Baiocchi R, Chaganti S, et al. New and updated results from a multicenter, open-label, global phase 3 (P3) study of tabelecleucel (tab-cel) for Epstein–Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) following allogeneic hematopoietic cell (HCT) or solid organ transplant (SOT) after failure of rituximab (R) or rituximab and chemotherapy (R+CT) (ALLELE). Presented at: 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.February 15-19, 2023; Orlando, FL. Abstract 25