Donor-Derived CAR T-Cell Therapy Yields High CR Rate With Limited OS in T-Cell Lymphoma After Allo-HSCT Relapse

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Treatment with a donor-derived, CD7-directed CAR T-cell therapy led to a high complete remission (CR) rate in patients with relapsed/refractory T-cell lymphoma who relapsed following allogeneic hematopoietic stem cell transplant (allo-HSCT), according to data from a phase 1 trial (ChiCTR2200058969) presented at the 51st Annual EBMT Meeting.

However, lead study author Fan Yang, MD, explained that the significant risk of infections and relapses in later stages of T-cell lymphoma affected survival rates.

Findings showed that evaluable patients (n = 17) achieved a CR rate of 94.1%; the only patient not to experience a CR had progressive disease. However, at a median follow-up of 8 months, only 6 of 17 patients were still alive, including 5 who remained in CR and 1 whose disease relapsed.

“The main causes of death were disease progression and infections, which were due to long-lasting cytopenias,” said Yang, who is the associate director of the Adult Lymphoma/Myeloma Department and master of medicine at Beijing GoBroad Boren Hospital in China.

After receiving CAR T-cell therapy, 5 patients (29.4%) were bridged to a second allo-HSCT from a different donor. Among these patients, 2 were still alive and disease-free at data cutoff; 1 was alive after disease relapse; and 2 died after relapse.

Regarding safety, cytopenias were reported in 94.1% of patients, and 31.3% of patients experienced a persistent cytopenia lasting more than 1 month. Viremia occurred in 82.4% of patients; this included cytomegalovirus (71.4%), Epstein–Barr virus (57.1%), and human herpesvirus 6 (28.6%).

Any-grade cytokine release syndrome (CRS) occurred in 94.1% of patients, and the rate of grade 3 or higher CRS was 12.5%. No instances of immune effector cell–associated neurotoxicity syndrome were reported. Grade 4 intestinal acute graft-vs-host disease was reported in 11.8% of patients.

Phase 1 Study Breakdown

Investigators enrolled patients with relapsed/refractory T-cell lymphoma who experienced disease relapse following allo-HSCT. Prior to enrollment, patients needed to have confirmed CD7-positive disease per tumor tissue sampling. Patients were enrolled between August 2020 and April 2024.

Unlike autologous CAR T-cell therapies, where T cells are derived from the patient, the CD7-targeted CAR T-cell therapy evaluated in this study was derived from a patient’s prior donor used for the allo-HSCT.

Upon enrollment, patients were allowed to undergo bridging chemotherapy, and lymphocytes were collected from the donor. During the 1-week manufacturing, patients underwent 3 days of lymphodepleting chemotherapy consisting of 300 mg/m² of cyclophosphamide per day and 30 mg/m² of fludarabine per day. The CAR T-cell therapy was then infused at a median dose of 1 x 10⁵ cells/kg (range, 0.16-24).

In an attempt to overcome fratricide, superficial T-cell antigen expression was limited via post-translational modifications.

Enrolled patients had a median age of 29 years (range, 19-53), and the majority were male (88.2%). Histologies included T-cell lymphoblastic lymphoma (88.2%), hepatosplenic T-cell lymphoma (5.9%), and extranodal NK/T-cell lymphoma (5.9%). Large mediastinal masses were reported in 29.4% of patients at baseline, 47.1% had bone marrow invasion, and 23.5% had central nervous system involvement.

Regarding prior allo-HSCT, donor types included haploidentical donor (64.7%), matched-unrelated donor (23.5%), and matched sibling donor (11.8%). The median time from relapse after allo-HSCT to CAR T-cell therapy was 4 months (range, 1-7). Additionally, 52.9% of patients received bridging therapy during the study. At the time of CAR T-cell therapy infusion, 23.5% of patients were in CR, 11.8% were in partial remission, and 64.7% were not in remission.

Pharmacokinetic Data

Additional findings showed the median peak time of expansion for CD7-positive CAR T cells in the peripheral blood was 9.5 days (range, 3-15). The median peak kinetics of CD7-positive CAR T cells measured by flow cytometry was 92.7 x 10⁶ cells/L (range, 7.17-1040). T cells remained detectable in 5 patients beyond 90 days, including 1 patient who had detectable T cells at 575 days.

The median time for CD7-positive lymphocyte levels to fall below the lower limit of detection was 11 days after infusion. CD7-positive lymphocytes were detected in the peripheral blood from 30 days after infusion.

Reference

Yang F, Liu R, Fu Z, et al. Efficacy and toxicity of donor-derived chimeric CD7 antigen receptor T-cell therapy in patients with T-cell lymphoma who relapse after allogeneic transplantation. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS10-03.