Dual-Target CD19/CD20 CAR T-Cell Therapy Achieves 63.6% Complete Remission Rate in R/R B-NHL
The overall response rate for the 11 treated patients was 72.7% at 3 months posttreatment.
A dual-target mCD19/hCD20 chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated a 63.6% complete remission (CR) rate in a study that treated 11 patients with relapsed/refractory (r/r) B-cell nonHodgkin lymphoma (B-NHL).1 The data were presented in a poster at the European Hematology Association (EHA) 2025 Congress, held June 12 to 15, both virtually and in Milan, Italy, by Liu Rui, of the Department of Lymphoma and Myeloma Research Center, at Beijing Gobroad Hospital, in Beijing, China.
The overall response rate for the treated patients was 8 out of 11 (72.7%) at 3 months posttreatment, with 7 patients (63.6%) having achieved at CR at this time point. Furthermore, Rui and colleagues reported that median overall survival and median progression-free survival were not reached at a median follow-up of 20.42 months. It was additionally noted that a median peak expansion value of 6,696 copies was observed, and that 7 days posttreatment constituted the median time to peak expansion.
With regard to safety, cytokine release syndrome (CRS) occurred in 7 of 11 patients (63.6%). There were no cases of CRS assessed as grade 3 or higher in severity. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in the study.
“Dual-target CAR-T therapy introduces an innovative treatment strategy for hematologic malignancies,” Rui and colleagues wrote in the poster’s introduction section.1 “CD19 and CD20 are the most representative targets in B-cell-associated tumors, with high coexpression in B-cell malignancies. Single-target therapies may lead to resistance due to antigen loss, whereas dual-target design mitigates the risk of antigen escape by simultaneously targeting CD19 and CD20, thereby enhancing treatment efficacy. Additionally, dual-target CAR-T therapy offers potential synergistic effects, improving tumor cell clearance. Studies have demonstrated promising preclinical and early clinical trial results in r/r B-NHL, laying the foundation for further investigations into its safety and efficacy.”
The ages of the patients treated in the study ranged from 28 to 74 years (median, 57). The group included 4 men (36.4%) and 7 women (63.6%). Two of the 11 patients (18.2%) had Eastern Cooperative Oncology Group performance scores of 2 or greater. The types of B-NHL represented included diffuse large B-cell lymphoma (LBCL) in 6 patients (54.5%), follicular lymphoma in 1 patient (9.1%), primary central nervous system lymphoma in 1 patient (9.1%), secondary central nervous system lymphoma in 2 patients (18.2%), and transformed follicular lymphoma in 1 patient (9.1%). Patients had received between 1 and 6 previous lines of treatment (median, 3). Autologous transplantation and prior CAR-T therapy were not among the previous treatment lines received by any of the patients.
A dose of 1x106 cells/kg was used for all patients for the the dual-target CAR-T. Treatment took place between June 2022 and September 2024 (inclusive).
“Dual-target CD19/CD20 CAR-T therapy demonstrated favorable safety and efficacy in r/r B-NHL, with good tolerability and no severe adverse events observed,” Rui and colleagues concluded.1 “These findings highlight its potential as a promising therapeutic strategy warranting further investigation.”
The dual-target CAR-T discussed in the poster is among many currently in development by various institutions and companies. Earlier this year, CGTLive® spoke with Sarah Larson, MD, the medical director of the Immune Effector Cell Therapy Program in the Division of Hematology/Oncology at David Geffen School of Medicine at University of California, Los Angeles (UCLA), about Lyell Immunopharma’s IMPT-314, a CD19/CD20 dual-targeted autologous CAR-T therapy, which is currently being evaluated in a phase 1/2 clinical trial (NCT05826535) for the treatment of relapsed/refractory LBCL in patients who have not previously received CAR-T therapy.2 Larson discussed the rationale behind the design of IMPT-314 and then went over some initial results from the trial.
“The results are very favorable, with an overall response rate of 94% and a complete response rate of 71%,” Larson told CGTLive. “These very promising efficacy results were also accompanied by a very favorable toxicity profile. Only grade 1 and 2 CRS were noted—there was no grade 3 CRS—and ICANS was predominantly grade 1/2, as well. The 3 patients that developed grade 3 ICANS resolved without any intervention above what's used in standard-of-care."
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