Dr Caimi on Early Data for LMY-920 in R/R B-Cell NHL

Paolo Caimi, MD, discusses the rationale behind evaluating LMY-920, a novel BAFF CAR T-cell therapy, in relapsed/refractory non-Hodgkin lymphoma.

Because [LMY-920 targets] the ligand for [the BAFF] receptor, it also shares several receptors, including BCMA and TACI, [meaning] that if you have a ligand that can bind to multiple receptors and lymphocytes, it's essentially acting like a multi-specific CAR T-cell therapy."

Paolo Caimi, MD, staff physician, Cleveland Clinic, associate professor, Department of Medicine, Division of Hematology and Oncology, School of Medicine, Case Western Reserve University, member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses the rationale behind and early data from a phase 1 trial (NCT05312801) evaluating LMY-920, a novel transposon-engineered BAFF ligand–based CAR T-cell therapy, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

Findings presented at the 2024 SITC Annual Meeting showed that among the first 3 patients treated during the study, 1 patient with transformed follicular achieved a complete response. A mixed response and stable disease were reported in 2 additional patients with mantle cell lymphoma. One of these patients experienced cytokine release syndrome, and no instances of immune effector cell–associated neurotoxicity syndrome were reported.

LMY-920 is designed to target multiple receptors critical to the survival and proliferation of lymphoma cells, Caimi explains. Unlike traditional CAR T-cell therapies that rely on a single-chain variable fragment, LMY-920 utilizes BAFF as its ligand, enabling it to act as a multi-specific CAR T-cell therapy, he adds, noting that this approach may help overcome antigen escape mechanisms. Transposon-engineered products can also be less expensive to produce compared with other traditional CAR T-cell therapies, Caimi continues, explaining that these types of CAR T-cell therapies could still be efficacious and less toxic, although clinical testing will need to validate efficacy and safety.

Although data are still early, preliminary results underscore the potential for LMY-920 to address critical limitations of existing CAR-T therapies, and further investigations will assess its clinical efficacy, safety, and broader applicability across hematologic malignancies, Caimi concludes.