Results are summarized here from a first-in-human, phase 1, dose-escalation study (NCT04938115) that evaluated the safety and efficacy of the novel CD7 chimeric antigen receptor (CAR)-T therapy in patients with refractory/relapsed CD7-positive mixed phenotype acute leukemia (MPAL).
The study enrolled adult patients with CD7-positive acute myeloid leukemia (AML). T-cells were purified from patient peripheral blood mononuclear cells using CD3+ magnetic beads or CD4+ and CD8+ magnetic beads. The investigational agent consisted of a second-generation CD7 (single-chain variable fragment) CAR with a 4-1BB costimulatory domain and the intracellular component of the CD3ζ molecule. Prior to the CAR T-cell infusion, patients received systemic bridging chemotherapy followed by intravenous fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) lymphodepleting chemotherapy for 3 consecutive days (day ─5 to day ─3). The median time from leukapheresis to CAR T-cell infusion was 14 days.
A total of 5 adult patients were enrolled in the study; of these, 4 patients had MPAL, 1 had FLT3-mutated AML. All 5 patients were infused with CD7 CAR T-cells, 1 patient received a low dose (1.5 × 105/kg), 1 received a medium dose (5.0 × 105/kg), and 3 received high-dose infusion (1.0 × 106/kg). At data cutoff, the median follow-up time was 127 days. The median age of the 5 patients was 33 years; the baseline median bone marrow blast percentage by morphology was 28.0%. Four patients had undergone prior allogeneic hematopoietic stem-cell transplantation (allo-SCT); of these, 1 patient had extramedullary disease (EMD), relapsed after a second transplant, and had also received CD19 CAR-T therapy. The median time from prior transplant to CD7 CAR T-cell infusion was 16 months.
On day 28 post-infusion, 4 of the 5 enrolled patients achieved complete remission (CR) or CR with incomplete blood recovery in bone marrow, and all 4 patients achieved minimal residual disease─negative CR. Remission was not achieved in the one patient with EMD, who withdrew on day 35. All 4 responders went on to receive consolidative allo-SCT after a median time of 11.3 weeks and remained in leukemia-free status for 19 weeks post-CAR T-cell infusion.
All 5 patients developed cytokine release syndrome (CRS); of these, 3 patients had grade 1 CRS, 1 patient had grade 2 CRS, and 1 patient had grade 3 CRS. There were no reports of neurotoxicity. Post–CAR-T therapy, grade 1 graft-versus-host disease was developed by 1 of 4 patients who had prior allo-SCT.
Based on these results, it was concluded that CD7-targeted CAR-T therapy was associated with a manageable safety profile and produced CRs in patients with CD7-positive MPAL, even in those who relapsed post-allotransplantation.
Source: Zhang X, et al. ASH 2021; abstr 1741.