CAR T cells manufactured within 24 hours safe, active in advanced B-cell ALL
Click Here to Manage Email Alerts
An investigational chimeric antigen receptor T-cell therapy showed antitumor activity among patients with relapsed or refractory B-cell acute lymphoblastic leukemia, according to data presented at the virtual ASH Annual Meeting and Exposition.
The novel dual-targeting CAR T-cell therapy was manufactured in less than 24 hours.
GC022F (Gracell Biotechnologies) — an autologous, bispecific CD19/CD22-targeted CAR T-cell therapy — is manufactured using Gracell’s proprietary FasT CAR platform.
“Shorter manufacturing time and lower cost are crucial for the wider application of CAR T-cell immunotherapy,” Peihua Lu, MD, director of the Lymphoma and Multiple Myeloma Center at Lu Daopei Institute of Hematology in Beijing, said during a presentation.
Preclinical studies using the FasT CAR technology showed the cells it produced to be more potent than those produced through a traditional cell culture process used in control models that took between 9 and 14 days.
The FasT CAR system brought the cell culture time down to less than 24 hours. This substantially reduced manufacturing time, according to Lu, who added that cells produced using FasT CAR still require the same quality control testing time required of traditional CAR T cells.
Lu and colleagues conducted a phase 1 study to determine the safety and tolerability of GC022F among patients with relapsed or refractory B-cell ALL.
The study enrolled 11 patients (mean age, 11 years; range, 3-48; n = 6 male) who received the therapy at one of three dose levels:
- low dose, 6.25 × 104 cells/kg (n = 2);
- medium dose, 1.49 × 105 cells/kg (n = 7); or
- high dose, 2.28 × 105 cells/kg (n = 2).
Seven patients had bone marrow blasts greater than 5% (range, 7-73).
CAR T cells were successfully manufactured for all patients in the study. Median CAR T-cell transduction efficiency was 29.8% (95% CI, 17-60.1).
All patients received a lymphodepletion regimen of IV fludarabine dosed at 25 mg/m² daily and cyclophosphamide dosed at 250 mg/m² daily for 3 days before infusion with GC022F.
Median follow-up was 126 days (range, 14-279) as of data cutoff Nov. 4.
Six of the patients with bone marrow blasts greater than 5% had a complete response to therapy and achieved minimal residual disease (MRD)-negative status by day 28 after infusion. One patient with bone marrow blasts greater than 5% had no response to therapy.
Among the four patients with less than 5% bone marrow blasts, three had an MRD-negative complete response to therapy by day 28 after infusion and one had persistent MRD positivity at day 14 after infusion.
Six of the study participants underwent subsequent allogeneic hematopoietic stem cell transplantation. Five of these patients maintained an MRD-negative complete response to therapy, whereas one died of graft-versus-host disease and infection.
Only one of the five patients who did not undergo allogeneic HSCT remained in MRD-negative complete response at 4 months after CAR T-cell infusion.
Treatment-related adverse events were manageable and mostly hematologic in nature.
Grade 3 or higher adverse events included leukopenia (n = 11), lymphopenia (n = 10) and neutropenia (n = 8).
Seven patients had cytokine release syndrome (CRS), including one patient with grade 3 or higher CRS. Median time to onset of CRS was 6 days (range, 3-19), with median duration of 8 days (range, 3-11).
Two patients(18%) experienced grade 1 immune effector cell-associated neurotoxicity syndrome.
“Our early clinical data demonstrate that GC022F had a favorable safety profile and good efficacy,” Lu said.
This novel CD19/CD22 CAR T-cell therapy, developed with the FasT CAR platform, could reduce the cost of treatment while delivering it faster, which is crucial for fast-progressing diseases such as the aggressive type of ALL seen in this study of mostly pediatric patients, according to Lu.
More data on additional patients and longer follow-up are needed to further evaluate the efficacy of this novel CAR T-cell therapy, Lu said.
Collapse
Yang J, et al. Abstract 159. Presented at: ASH Annual Meeting and Exposition (virtual meeting); Dec. 5-8, 2020.
Click Here to Manage Email Alerts