BAFF-R–Targeted CAR T Therapy Shows Durable Complete Responses in Relapsed B-Cell Lymphoma
Clinical Summary:
- Design/Population: This multicenter phase 1 dose-escalation study evaluated PMB-CT01, an investigational BAFF-R–targeted CAR T-cell therapy, in adults with relapsed or refractory B-cell non-Hodgkin lymphoma, including patients previously treated with CD19-directed CAR T-cell therapy.
- Key Outcomes: PMB-CT01 demonstrated a favorable safety profile, a high complete response rate, and durable remissions, including among patients with prior CD19-directed CAR T-cell therapy and CD19/CD20-negative disease.
- Clinical Relevance: These findings support BAFF-R as a promising CAR T-cell target and suggest a potential strategy to overcome antigen escape following CD19-directed CAR T-cell therapy.
Results from a phase 1 study demonstrated that PMB-CT01, an investigational BAFF-R–targeted CAR T-cell therapy, elicited durable complete responses with a favorable safety profile in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
These results were presented by L. Elizabeth Budde, MD, PhD, of City of Hope National Medical Center in Duarte, California, at the European Hematology Association (EHA) Congress in Stockholm, Sweden.
In this multicenter trial, 9 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including mantle cell lymphoma (n = 6), large B-cell lymphoma (n = 1), follicular lymphoma (n = 1), and marginal zone lymphoma (n = 1), received a single infusion of PMB-CT01 following standard lymphodepletion at either 50 × 106 CAR-positive T cells (dose level 1; n = 3) or 200 × 106 CAR-positive T cells (dose level 2; n = 6). Patients had received a median of 3 prior therapies, including prior CD19-directed CAR T-cell therapy (n = 6) and a T-cell engager (n = 3). The primary end points were safety, dose-limiting toxicities, and determination of the recommended phase 2 dose. Secondary end points included antitumor activity and survival outcomes.
No dose-limiting toxicities were observed at either dose level. Cytokine release syndrome occurred in 78% of patients, with all events limited to grade 1. Two patients experienced grade 1 immune effector cell-associated neurotoxicity syndrome, both of which resolved without corticosteroid treatment.
Seven patients achieved complete responses, including patients previously treated with CD19-directed CAR T-cell therapy and those with CD19/CD20-negative disease, while 2 patients achieved stable disease. Robust CAR T-cell expansion was observed in all responders, and all responding patients with mantle cell lymphoma (n = 4) achieved minimal residual disease negativity.
At a median follow-up of 22 months, all patients were alive, and all complete responses remained ongoing without relapse. Based on these findings, dose level 2 (200 × 106 CAR-positive T cells) was selected as the recommended phase 2 dose.
"Completion of the dose-escalation portion of this phase 1 trial demonstrated a favorable safety profile and durable complete responses with BAFF-R-targeted CAR T-cell therapy...including those with prior CD19 CAR T-cell failure or CD19-negative disease," concluded Dr Budde. "These results supported the selection of the recommended phase 2 dose and initiation of disease-specific expansion cohorts."
Source:
Budde LE, Del Real M, Macias A, et al. Durable responses and favorable safety of BAFF-R CAR T-cells (PMBCT01) in patients with relapsed/refractory B-cell lymphomas with prior CD19-directed therapy failure or CD19-negative disease. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-1611.
