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CAR T cells appear effective in leukemia subtype
ATLANTA — Chimeric antigen receptor T cells have been at the forefront of immunotherapy for the treatment of B-cell malignancies, according to Amelia A. Langston, MD, medical director and section chief of the Bone Marrow and Stem Cell Transplant Program at the Winship Cancer Institute.
“But, the greatest success that’s been published to date has been in children with acute lymphoblastic leukemia,” Langston said.
Langston spoke with HemOnc Today after Bijal D. Shah, MD, presented updated results of the ZUMA-3 trial, which analyzed the use of KTE-C19 (Kite Pharmaceuticals) in adults with high-burden relapsed or refractory acute lymphoblastic leukemia.
As previously reported by HemOnc Today at the ASCO Annual Meeting, the ongoing phase 1 study has demonstrated a generally manageable safety profile and appears effective in the adult patient population.
Twenty-two patients had been enrolled at the data cut-off date of April 26, 2017, of which 16 had received KTE-C19.
Patients received a target dose of 1 × 106 CAR T cells/kg (n = 10) or 2 × 106 CAR T cells/kg (n = 6) after lymphodepletion with 25 mg/m2/day fludarabine for 3 days and 900 mg/m2/day cyclophosphamide given on the last day.
Incidence of dose-limiting toxicities served as the primary endpoint. Secondary endpoints included the incidence of adverse events, the incidence of minimal residual disease-negative responses, duration of remission, RFS, and OS.
Four patients had not received treatment by data cut-off, one patient did not receive study drug due to an adverse event after conditioning, and one patient received treatment under compassionate use.
Nineteen percent of patients had undergone prior allogeneic stem cell transplant, 31% had relapsed or refractory disease to at least second-line therapy, 31% had primary refractory disease, and 19% experienced first relapse within 12 months of first remission.
The researchers did not observe any dose-limiting toxicities.
One patient who received the 2 × 106 cells/kg dose experienced a grade 5 event of cytokine release syndrome. No other therapy-related grade 5 adverse events occurred.
Patients who received KTE-C19 were followed for at least 3 weeks. The most common grade 3 or higher adverse events included hypotension (56%), anemia (50%), pyrexia (50%), and decreased platelet counts (44%).
Objective response rate was 82% among the 11 patients eligible for efficacy analysis. Eight of those patients had a complete remission, and one had blast-free bone marrow.
All remissions were minimal residual disease-negative as determined by flow cytometry.
Four patients relapsed between 63 and 168 days after completing treatment with KTE-C19.
“I think it’s too soon to tell how durable these remissions will be,” Langston said. “There have been four patients in the cohort who have already relapsed with fairly short follow-up. This may not be a stand-alone therapy, but it may be a bridge to allogeneic transplantation which can be curative for a substantial fraction of these patients.”
Although it may be too early to see how durable these remissions will be, Langston said that it’s just the beginning.
“We are just at the beginning in terms of understanding how to optimize these adoptive T-cell technologies and there are now second and third and fourth generation CARs that are being developed that will likely be more effective,” Langston said. “There may be CAR T-cell approaches that may involve more than one target or that involve combination with other immune-stimulants, so I think we’re just at the beginning of seeing where that field can go.”
Reference:
Shah BD, et al. Abstract 888. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Langston reports research funding through her institution from Kite Pharmaceuticals and Novartis. Shah reports no relevant financial disclosures.