Dr Bishop on the Rationale for Evaluating Anito-Cel in R/R Myeloma

“[Anitocabtagene autoleucel] is a synthetic binder [that] is different than almost any CAR T-cell therapy because most receptors on CAR T cells are derived from a monoclonal antibody.”

Michael R. Bishop, MD, a professor of medicine and director of the Hematopoietic Stem Cell Transplantation Program at The University of Chicago Medicine, explained the rationale for evaluating anitocabtagene autoleucel (anito-cel) for the treatment of patients with relapsed/refractory multiple myeloma.

In a phase 1 trial (NCT04155749), the autologous D-domain, BCMA-directed CAR T-cell therapy anito-cel was investigated in patients with relapsed/refractory multiple myeloma, Bishop began. He noted that the FDA guided the study, notably because the CAR T-cell therapy has a synthetic binder. This is a unique feature compared with most CAR T-cell therapies, as most receptors on CAR T-cells are derived from monoclonal antibodies, he said. With anito-cel, the synthetic binder could target BCMA, Bishop added. He emphasized that the study was originally planned to be an adaptive study; however, the FDA aimed to demonstrate the functionality of the receptor in a CAR T-cell therapy—the rationale for the study.

At a median follow-up of 38.1 months, treatment-emergent adverse effects (TEAEs), the study’s primary objective, included no delayed or non–immune effector cell–neurotoxicity syndrome (ICANS) neurotoxicities occurred, including no observed cases of Parkinsonism, Guilliain-Barré syndrome, or cranial nerve palsies.

Early efficacy findings from the study revealed that patients treated with anito-cel achieved an overall response rate of 100%, including 79% of patients achieving a complete response (CR) or stringent CR. Of note, 13% of patients achieved a very good partial response, with 8% demonstrating a partial response. Minimal residual disease negativity at a sensitivity threshold of 10–5 was achieved in 89% of evaluable patients.

Patients included on the study had relapsed/refractory multiple myeloma and were previously treated with at least 3 lines of therapy, which included a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, or those who had triple-refractory disease after treatment of these 3 classes of drugs.

Based on the findings, the study investigators were surprised to determine that the binder worked well regarding efficacy and safety, Bishop concluded.