AB-205, an engineered cell therapy, showed efficacy and safety in adult patients with lymphoma undergoing high-dose therapy (HDT) and autologous hematopoietic stem cell transplantation (AHCT). Results of an open-label dose escalation trial were reported at the 2021 Transplantation and Cellular Therapy Meetings.
The authors noted that HDT-AHCT is the standard potentially curative therapy for aggressive lymphoma. Although there have been significant improvements in care using HDT-AHCT, there is still a risk of the patient developing severe regimen-related toxicities (SRRTs) which can limit the use of this therapy. SRRTs often consist of nausea, vomiting, diarrhea, and severe mucositis leading to high symptom burden. These can lead to an increased risk for serious complications.
The experimental therapy AB-205 consists of genetically engineered allogeneic E4+ human umbilical vein endothelial cells and is currently being investigated in patients with lymphoma undergoing HDT-AHCT. The therapy is designed to accelerate regeneration of organs in order to eliminate or reduce SRRTs. “Preclinical studies of [allogeneic E4+ human umbilical vein endothelial cells] infused after conditioning have shown accelerated recovery of multiple organ functions,” the authors wrote in their abstract.
As of August 18, 2020, a total of 35 participants were treated with AB-205. They were divided into 2 groups based on their disease type: systemic lymphoma (28 patients) and central nervous system (CNS) lymphoma (7 patients). The median ages were 53 and 59 years, respectively, and 63% and 43% were men, respectively. A retrospective chart review of 45 patients at a participating site served as the comparative control group.
The objectives for the study were safety and assessment of grade 3 or higher adverse events (AEs), oral and gastrointestinal SRRTs, and time to engraftment.
AB-205 was administered intravenously on the same day as AHCT (day 0) in 3 dose-escalated cohorts: 5, 10, and 20×106 cells/kg. The highest level was given either as single dose or split into equal doses on day 0 and day 2.
Reported AEs were generally mild or moderate and expected with HDT-AHCT. One patient had disease relapse during the study period. Therapy with AB-205 demonstrated dose-dependent reduction of all grade and grade 3 or higher AEs. Additionally, there was trend for a dose-dependent decrease in the incidence of febrile neutropenia. The median time to neutrophil and platelet engraftment was 10 and 11 days in the systemic lymphoma and CNS lymphoma groups, respectively. A total of 71% of patients had platelet engraftment within 1 day after neutrophil engraftment.
The highest dose AB-205 eliminated grade 3 or higher oral and gastrointestinal SRRTs in patients with systemic lymphoma undergoing HDT-AHCT, along with dose-dependent reductions in all-grade oral and gastrointestinal toxicities. These results compare favorably to the event rate of the control group.
Disclosure: Several study authors declared affiliations with the biotech or pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.
Budde LE, Scordo M, Abedi M, et al. Results of an open label dose escalation trial of AB-205 (E-CEL® cells) in adults with lymphoma undergoing high-dose therapy and autologous hematopoietic cell transplantation (HDT-AHCT) [TCT Abstract 27]. Transplant Cell Ther. 2021;3S(suppl):S26-S27. doi:10.1016/S2666-6367(21)00053-1