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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 

 evaluating LMY-920, a novel transposon-engineered BAFF ligand–based CAR T-cell therapy, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

 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.

Videos

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

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

Paolo F. Caimi, MD, associate professor, Department of Medicine, Division of Hematology and Oncology, School of Medicine, member, Immune Oncology Program, Case Comprehensive Cancer Center, medical director, Clinical Trials Unit, University Hospitals Seidman Cancer Center, physician, Department of Hematology and Oncology, University Hospitals Cleveland Medical Center, discusses the FDA approval of loncastuximab tesirine-lpyl (Zynlonta) in relapsed/refractory large B-cell lymphoma (LBCL).

On April 23, 2021, the FDA granted an accelerated approval to loncastuximab tesirine for the treatment of patients with relapsed/refractory LBCL, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma, following 2 or more lines of systemic therapy.

The regulatory decision was based on findings from the phase 2 LOTIS-2 trial (NCT03589469), in which loncastuximab tesirine elicited a 48.3% objective response rate, including a 24.1% complete response rate, in this patient population.

Loncastuximab tesirine is a CD19-directed antibody and alkylating agent conjugate that carries a chemotherapy warhead, Caimi says. The approval of the agent offers a single-agent, off-the-shelf option that is not associated with neuropathy for patients with relapsed/refractory LBCL, Caimi explains. Moreover, this patient population benefits from having multiple agents available that target the same antigen, such as CD19, in different modalities, Caimi concludes.

Paolo F. Caimi, MD, discusses the FDA approval of loncastuximab tesirine-lpyl in relapsed/refractory large B-cell lymphoma. 



Paolo F. Caimi, MD

Articles

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

Dr. Caimi on the FDA Approval of Loncastuximab Tesirine in R/R Large B-Cell Lymphoma