Nonviral CAR-T is ‘remarkably safe’ and clinically active in B-cell ALL
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More than 60% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia achieved initial complete remission after receiving an investigational chimeric antigen receptor T-cell therapy, phase 1/phase 2 study results showed.
By their initial 1-month evaluation, 73% of patients who received the highest dose levels had a complete response to therapy, according to findings presented at European Society for Blood and Marrow Transplantation-European Hematology Association 4th European CAR T-cell Meeting.
Background
CARCIK-CD19 — an investigational therapy developed by scientists in Italy — comprises donor-derived CD19-targeted CAR T cells differentiated according to the cytokine-induced killer cell (CIK) protocol that uses nonviral Sleeping Beauty transposon gene transfer to prevent graft-versus-host disease.
“CAR T cells engineered with nonviral methods offer a modality to reduce costs and logistical complexity of the viral process,” Chiara F. Magnani, PhD, research scientist in the department of medical oncology and hematology at University Hospital Zurich, told Healio.
Magnani — who participated in the research while a member of the department of pediatrics at University of Milano-Bicocca’s Tettamanti Research Center in Monza, Italy — said that Sleeping Beauty-engineered CAR T cells were successfully produced for all patients using the peripheral blood of hematopoietic stem cell transplantation donors.
She described “robust” CAR T-cell expansion observed in most patients that could be measured in their blood for up to 2 years after infusion.
“CARCIK-CD19 infusion was remarkably safe in all treated patients and clinically active,” Magnani added.
Methodology
Magnani and colleagues enrolled 26 patients in the study, 21 (median age 36 years; range, 1-62; 52% female) of whom eventually received CARCIK-CD19 CAR T cells. The heavily pretreated study population received a median four (range, 1-7) previous lines of therapy and included four children and 17 adults.
Patients underwent lymphodepletion chemotherapy followed by CAR T-cell infusion at one of four dose levels: 1 × 106 (n = 3), 3 × 106 (n = 3), 7.5 × 106 (n = 3) or 15 × 106 (n = 12) CARCIK-CD19 cells/kg.
Researchers noted no dose-limiting toxicities during the study, which had a median follow-up of 2.05 years.
Key findings
Six patients (28.6%) who received the highest dose level experienced grade 1 or grade 2 cytokine release syndrome. No cases of grade 3 or higher CRS occurred during the study.
Two patients (10%) who received the highest dose level developed grade 3 immune effector cell associated neurotoxicity syndrome.
No patients developed GVHD after receiving CARCIK-CD19 CAR T cells despite nine of 21 patients in the study experiencing GVHD after a previous HSCT.
Six patients (28.6) developed infections after CAR-T infusion. Three patients (14%) developed grade 4 infections.
Treatment efficacy results showed 13 patients (61.9%; 95% CI, 38% to 82%) achieved a complete response to therapy, including 11 of 15 patients (73%; 95% CI, 45% to 92%) who received the two highest dose levels.
Patients who received the highest dose levels had a 6-month OS rate of 73% and a 1-year OS rate of 48%. The same group had EFS rates of 33% at 6 months and 22% at 1 year.
Cell donor type did not affect a patient’s ability to achieve a complete response to therapy as of the initial day 28 evaluation, according to the investigators.
Clincial implications
The durability of CARCIK-CD19 CAR T cells compared with commercially available autologous CD19-directed CAR-T is difficult to determine at this time because traditional CAR-T is typically followed by consolidation therapy with allogeneic HSCT, Magnani said.
Patients in this study already experienced disease progression after a previous transplant and did not receive any further anti-leukemic therapies unless a relapse occurred.
She said she does find encouragement in two children who underwent allogeneic HSCT after receiving CARCIK-CD19 CAR T cells and are currently in remission, in addition to two adults who remain in remission without additional therapy.
“At the highest dose levels, a substantial rate of response was achieved,” she told Healio. “[Our] data are comparable with currently available CAR T cells when considering the heavily pretreated patient population in our study.”
A phase 2 study evaluating CARCIK-CD1 CAR T cells is enrolling patients with relapsed or refractory B-cell ALL using “a residual disease-driven strategy,” Magnani said. Her group also anticipates initiating a separate study for the investigational cell therapy in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia.
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Magnani CF, et al. Abstract PT04-1. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 4th European CAR T-cell Meeting; Feb. 10-12, 2022.
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