This issue presents the latest research results from Dr. Kai Hu’s team at Beijing Gobroad Hospital, led by Dr. Fan Yang, on CD7 CAR-T cell therapy for relapsed or refractory T-cell lymphoma. The study was selected for poster presentation at the ASH 2025.
Background
Relapsed or refractory (R/R) T-cell lymphoma has extremely poor prognosis, especially among patients who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment options are limited and survival outcomes remain dismal.
Objective
This single-center Phase I study (ChiCTR2200058969) investigated CD7 CAR-T cell therapy to evaluate long-term safety, pharmacokinetics, tolerability, and efficacy in patients with R/R T-cell lymphoma.
Methods
CD7 CAR-T cells were generated from mononuclear cells using lentiviral transduction to introduce a CD7 CAR construct containing an endoplasmic reticulum–retention motif, preventing surface CD7 expression and avoiding fratricide among CAR-T cells.
The therapy was first assessed in a Phase Ia dose-escalation study using a 3+3 design, followed by a Phase Ib dose-expansion cohort. The three dose levels (DLs) were:
- DL1: 1×10⁴ CAR⁺ cells/kg
- DL2: 5×10⁴ CAR⁺ cells/kg
- DL3: 1×10⁵ CAR⁺ cells/kg (±30%)
Ia-phase data were used to determine the recommended Phase Ib dose. Donor-derived CAR-T cells were infused in patients who relapsed after allo-HSCT, while other patients received autologous CAR-T cells.
Results
Between August 2020 and August 2024, 48 patients were screened and 40 were enrolled. The median age was 32 years (range 18–72). Diagnoses included T-lymphoblastic lymphoma (T-LBL, n=35), hepatosplenic T-cell lymphoma (HSTL, n=1), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL, n=1), Sézary syndrome (n=1), extranodal NK/T-cell lymphoma (n=1), and cutaneous T-cell lymphoma (CTCL, n=1).
All patients had disease progression after multi-line therapies, including autologous HSCT (n=5) and allo-HSCT (n=17). A total of 24 patients (60%) had disseminated disease, and 8 patients (20%) had CNS involvement. To further reduce tumor burden, 34 patients (85%) received bridging therapy before CAR-T infusion.
During the dose-escalation stage, nine patients were sequentially assigned to DL1–DL3 (three per group), and no dose-limiting toxicities (DLTs) were observed. Thirty-one patients entered the Phase Ib expansion cohort at DL3.
Safety
Cytokine release syndrome (CRS) occurred in 80% of patients, including 7.5% with grade 3–4 CRS. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 2.5% (one grade 4 case). The most common treatment-related adverse events included neutropenia (77.5%; 75% grade 3–4), thrombocytopenia (65%; 62.5% grade 3–5), and infections (65%; 45% grade 3–4).
Two patients (5%) experienced grade 3–4 acute graft-vs-host disease (aGVHD), and two (5%) developed grade 2 immune effector cell–associated HLH-like syndrome (IEC-HS). Adverse-event rates were not significantly associated with CAR-T cell source (autologous vs donor-derived) (P=0.402).
Efficacy
Among the 40 evaluable patients, the 1-month overall response rate (ORR) was 92.5% (37/40) and complete response (CR) rate was 77.5% (31/40).
- Autologous CD7 CAR-T group (n=23): ORR 86.9%, CR 73.9%
- Donor-derived group (n=17): ORR 100%, CR 82.4%
With a median follow-up of 16.34 months (95% CI: 1.78–48.07), the overall 3-year progression-free survival (PFS) was 28.9% and overall survival (OS) was 36.3%.
Subgroup Findings
In the autologous group, the 3-year PFS was 31.3% and OS was 47%.
Fifteen patients (65.2%) underwent allo-HSCT as consolidation after achieving CR, with 9 patients (60%) remaining disease-free. One patient relapsed post-transplant but responded to further therapy; one died from relapse; four died due to infection or bleeding. Among seven patients who did not undergo transplant, one (14.3%) remained disease-free.
In the donor-derived group, the 3-year PFS was 20.6% and OS was 28.2%.
Among four patients who received consolidative allo-HSCT, one achieved long-term remission; two died from relapse, and one died from PTLD. Of the 13 patients without transplant, two remained disease-free, three died from relapse, seven died from infection, and one was lost to follow-up.
CAR-T Kinetics
CAR-T expansion was detected in all nine patients in Phase Ia. In Phase Ib, the median time to expansion peak was day 11 (range 7–21). The median CAR-T peak concentration in peripheral blood was 23.65×10⁶/L (range 1.56–219×10⁶/L), with no significant association with cell source (P=0.15). Despite depletion of CD7-positive T cells, CD7-negative T cells expanded in all patients.
Conclusion
CD7 CAR-T therapy demonstrated strong activity in patients with relapsed/refractory T-cell lymphoma. For patients receiving autologous CD7 CAR-T cells, consolidative allo-HSCT after achieving complete remission may further improve survival. However, for patients receiving donor-derived CD7 CAR-T cells after allo-HSCT relapse, risks of infection and disease recurrence remain high, highlighting the need for more effective post-remission strategies.
Orginal article: CD7 chimeric antigen receptor T cells for relapsed/refractory T-cell lymphomas: Single-arm, open-label, phase I study
