Bispecific anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was well tolerated and showed signs of clinical efficacy in patients with relapsed/refractory B-cell lymphoma, according to phase I clinical trial data presented by Ghafouri et al during week 1 of the virtual American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract CT007).
“Patients with relapsed/refractory B-cell lymphoma tend to have a more aggressive disease trajectory and limited treatment options,” said presenting author Sanaz Ghafouri, MD, a hematology and oncology fellow at the University of California Los Angeles Medical Center. “Anti-CD19 CAR T-cell therapy has revolutionized the management of this disease in recent years, but it still has several limitations,” she noted, explaining that approximately half of patients relapse within 6 months of starting treatment due to a lack of CAR T-cell persistence and/or downregulation of the target antigen, CD19, on the tumor.
“The prognosis of patients who relapse after CAR T-cell therapy is dismal,” added Dr. Ghafouri.
Anti-CD19/CD20 Bispecific CAR T-Cells
Bispecific CAR T-cells target two tumor antigens at once and have been explored as a strategy to reduce the risk of relapse. In this study, Dr. Ghafouri and colleagues evaluated the safety and efficacy of anti-CD19/CD20 bispecific CAR T-cells using naive memory cells.
“This is the first bispecific CAR T-cell therapy developed with naive memory T-cells to be tested in patients,” she said. “We hypothesized that this approach might increase CAR T-cell persistence and expansion in patient[s], while limiting relapses due to loss of the tumor antigen.”
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The presented analysis included five patients with B-cell malignancies that were positive for both CD19 and CD20 tumor antigen expression. Patients had received a median of four prior lines of therapy, and four patients had received bridging therapy. Naive memory T cells were extracted from each patient, engineered to express an anti-CD19/CD20 CAR, expanded, and infused back into the patient at one of two different doses (either 5 × 107 cells or 2 × 108 cells).
Responses
After a median follow-up of 13 months, four of the five patients had ongoing complete remission. The patient whose cancer did not respond to treatment had early disease progression with CD19/CD20-negative disease by day 14 after infusion. Median progression-free and overall survival were not reached at the time of follow-up, and all responding patients continued to have CAR T-cell persistence at the time of data cutoff.
No dose-limiting toxicities or immune effector cell–associated neurotoxicity were observed in any of the patients. All patients had grade 1 cytokine-release syndrome, and all responding patients had ongoing B-cell aplasia at the time of data cutoff.
“Although long-term follow-up and analysis of additional patients are needed, our results indicate that bispecific anti-CD19/CD20 CAR in naive memory T cells may be safe and effective in patients with relapsed or refractory B-cell lymphomas,” said Dr. Ghafouri. “Our findings raise the possibility of a lasting long-term remission with bispecific CAR T-cell therapy in patients with this aggressive disease.”
Dr. Ghafouri and colleagues plan to expand their patient cohort and are also interested in evaluating the therapy in additional B-cell lymphoma subtypes.
Limitations of the study include the small sample size and lack of long-term follow-up.
Disclosure: The study was supported by the Parker Institute of Cancer Immunotherapy and a donation from Stephen and Joan Kaplan. For full disclosures of the study authors, visit abstractsonline.com.
