CD7 CAR T-Cell Therapy in Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia: A Retrospective Study

Introduction

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have poor outcomes due to limited effective treatment strategies. CD7 CAR T therapy has been shown to be a promising salvage option for r/r T-ALL patients. To identify prognostic factors for survival in r/r T-ALL patients treated with CD7 CAR T-cell therapy, we performed a retrospective analysis combining the results of two clinical trials.

Method

This is a retrospective analysis of donor-derived CD7 CAR T-cell therapy in r/r T-ALL, based on a phase 1 trial (ChiCTR2000034762) and a phase 2 trial (NCT04689659). Both the two trials were approved by Institutional Review Board of Beijing Goboard Boren Hospital. Event-free survival (EFS) was defined as the time from CAR T infusion to the earliest date of treatment failure, relapse, progression, MRD emergence, or death from any cause. SCT was not censored in the derivation of EFS. Overall survival (OS) was defined as the time from CAR T infusion to death from any cause. The Kaplan-Meier estimator was used for EFS and OS, with the log-rank test used for comparisons in univariable analysis and COX regression model for multivariable analysis.

Results

A total of 75 patients were included in this analysis, including 20 from the phase 1 trial and 55 from the phase 2 trial. The median age of the 75 patients was 12 (range 2-43). 55 patients (73%) were male, and 20 (27%) were female. All patients were Asian. At baseline, the median tumor burden in bone marrow (BM) was 5.77% (range, 0-87.99), as determined by flow cytometry. 11 (15%) had central nervous system leukemia (CNSL), and 41 patients (55%) had non-CNS extramedullary diseases (EMDs). Patients had received a median of 4 (range, 2-10) lines of previous therapy. 50 patients (67%) received prior-SCT donor-derived CD7 CAR T cells following standard lymphodepletion, and 25 (33%) received newly HLA-matched donor-derived CD7 CAR T cells following intensified lymphodepletion. 26 (35%) had received SCT consolidation post CD7 CAR. The EFS and OS rate at 24 months were 26% (95% confidence interval [CI], 17-41) and 29% (95%CI, 19-45), respectively.

In the univariable analysis, the 24-month EFS and OS rate were 51% (95%CI, 34-76) and 51% (95%CI, 33-78) in patients with SCT consolidation, significantly higher than 11% (95%CI, 4-21 p=0.003) and 15% (95%CI, 7-35, p=0.003) in patients without; 21% (95%CI, 11-43) and 22% (95%CI, 11-43) in patients with non-CNS EMDs, significantly lower than 34% (95%CI, 20-60, p=0.028) and 40% (95%CI, 24-68, p=0.010) in patients without. Patients with >5% but ≤50% blasts in BM had higher EFS and OS rate than patients with ≤5% blasts (p=0.001 for EFS, p=0.004 for OS) and patients with >50% blasts (p<0.001 for EFS, p=0.023 for OS). Patients with ≤4 lines of prior therapy had significantly higher OS rate than patients with >4 (p=0.018), but a comparable EFS rate. No significant difference in EFS and OS rate in patient subgroups according to sex, age, donor source, CNSL, and infusion dose level. A multivariable COX regression model was constructed including six variables, namely non-CNS EMD, SCT consolidation, lines of prior therapy, age, dose level, and tumor load in BM. The results revealed that SCT consolidation (HR, 2.24, 95%CI 1.06-4.72, p=0.035) was significantly associated with superior EFS, while non-CNS EMD (HR, 0.45, 95%CI, 0.22-0.90, p=0.024), ≥5% but <50% blasts in BM (versus <5% blasts [HR, 0.38, 95%CI 0.18-0.84, p=0.016]), and ≥50% blasts in BM (versus <5% [HR, 0.16, 95%CI 0.06-0.42, p<0.001]) were significantly associated with inferior EFS. Non-CNS EMD (HR, 0.45, 95%CI, 0.21-0.95, p=0.036) and ≥50% blasts in BM (versus <5% blasts [HR, 0.32, 95%CI 0.12-0.91, p=0.033]) was significantly associated with inferior OS.

Conclusion

These data demonstrated that non-CNS EMD and bone marrow burden were independent risk factors for inferior survival in patients who received donor-derived CD7 CAR T therapy. SCT consolidation may exert a beneficial impact on them.