Genetic Engineering Publications - GEG Tech top picks

ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. The scientists evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. 

The first CAR-T immunotherapy directed against BCMA (idecabtagene vicleucel) for patients with relapsed or refractory multiple myeloma developed by partners Bristol Myers Squibb and bluebird bio was approved by the U.S. Food and Drug Administration on March 26, 2021.

This therapy recognizes and binds BCMA (B cell maturation antigen) which is a cell surface protein that is expressed on a majority of cancerous B cells in multiple myeloma. The approval is based on the KarMMa trial of 127 patients, 100 of whom received the personalized treatment with genetically engineered autologous T cells. Their overall response rate was 72%, and 28% achieved a strict complete response. For Bristol Myers Squibb, this is the second approval for a CAR-T cell therapy. The first was for a therapy directed against CD19.

Bristol Myers Squibb and bluebird will jointly market their immunotherapy at a list price of $419,500.

Clinicians treating patients with CAR T cells have become adept at identifying and treating acute neurotoxicity, a common adverse event associated with the therapy. Researchers at Mount Sinai published a case study in Nature Medicine of a patient who developed a neurocognitive, hypokinetic movement disorder with features of Parkinson's disease after receiving the CAR-T therapy targeting the B-cell maturation antigen (BCMA) called ciltacabtagene autoleucel in the CARTITUDE-1 clinical trial. Since reports of this toxicity have not been observed with CD19-directed CAR-T therapies for other blood cancers, it appears to be specifically associated with BCMA-directed CAR-T. As it turns out, Parekh and colleagues found that BCMA is expressed on certain brain cells, and they saw evidence that BCMA-targeted CAR-T cells entered the patient's cerebrospinal fluid and crossed the blood-brain barrier. With ciltacabtagene autoleucel poised to become the second BCMA-directed CAR-T to gain commercial approval later this year, clinicians should discuss the potential benefits and risks of the therapy with their patients. They also need to be vigilant about screening for late neurological toxicities until researchers can make improvements to the new CAR-T constructs to mitigate the risk.