A novel TRBC1-directed autologous CAR T-cell therapy has demonstrated encouraging efficacy in treating patients with relapsed or refractory peripheral T-cell lymphomas (PTCL), according to newly published results from the phase 1/2 LibraT1 trial in Nature Medicine.
The study, which evaluated the therapeutic agent AUTO4, showed promising responses in a cohort of nine evaluable patients. With a median follow-up of 13.8 months, researchers observed an overall response rate of 66.6%, including four complete metabolic responses (CMR) and two partial responses.
Impressive Response at Highest Dose Level
Particularly noteworthy results emerged from the highest dose cohort, where all four patients treated with 450 x 106 CAR T cells achieved objective responses. Among these patients, three achieved complete metabolic responses, with two maintaining their remission status at 15 and 18 months post-treatment.
"The preliminary efficacy and the ongoing responses reported in this phase 1 study are encouraging," stated Dr. Kate Cwynarski, Chair of the UK T Cell Lymphoma Working Group and associate professor at University College London. She emphasized the potential of AUTO4 CAR T therapy to "induce long-lasting remissions in a proportion of patients."
Study Design and Patient Characteristics
The trial enrolled 10 patients with a median age of 55 years, representing various PTCL subtypes: five with PTCL not otherwise specified (PTCL-NOS), four with angioimmunoblastic T cell lymphoma (AITL), and one with anaplastic large cell lymphoma (ALCL). Patients had received a median of two prior lines of therapy.
Treatment protocol included lymphodepletion with fludarabine and cyclophosphamide before AUTO4 infusion. The study evaluated four dose levels: 25 x 106, 75 x 106, 225 x 106, and 450 x 106 cells.
Safety Profile
The therapy demonstrated a manageable safety profile. Cytokine release syndrome (CRS) occurred in four patients, all at the highest dose level, with a median onset of one day and typical duration of two days. Only one patient experienced grade 3 CRS, which resolved within three days. Notably, no cases of immune cell-associated neurotoxicity syndrome (ICANS) or dose-limiting toxicities were reported.
Clinical Implications
These early results suggest that AUTO4 could potentially address an important unmet need in PTCL treatment, particularly for patients with relapsed or refractory disease. The sustained complete responses observed in some patients at the highest dose level are particularly encouraging for this difficult-to-treat patient population.
