CRP levels signal cytokine storm in CAR therapy

Efficacy

The complete response rate in the study was 88%, with 12 of these 14 patients further classified as having minimal residual disease. Seven (44%) patients were successfully bridged to allogeneic stem cell transplantation. This is "especially meaningful" when compared with the historic low of just 5% of relapsed/refractory adult B-ALL patients transitioning to transplant after salvage chemotherapy, Dr. Davila noted.

Still, the persistence of the 19-28z CAR T cells was about 3 months, compared with several months to even more than one year in at least one B-ALL patient and several CLL patients reported by the University of Pennsylvania researchers. Dr. Davila and his colleagues hypothesize that the longer persistence of CD19-targeted CARs incorporating a 4-1BB moiety, rather than CD28, may be due, in part, to antigen-independent signaling through the 4-1BB CAR, as previously shown in preclinical studies. They are also currently developing a human anti-mouse antibody assay to determine whether immune-mediated rejection might be a contributing factor to the limited persistence of the 19-28z CAR T cells.

Dr. Porter said it’s not known why their T cells persist longer, but agreed it may have to do with the novel signal domain of their CAR (4-1BB). "This may be important for high levels of expansion, but may also provide a survival signal to the T cells allowing for longer persistence," he said.

The study was supported by MSKCC. Dr. Davila reported having no financial disclosures. Dr. Brentjens holds a patent that covers the 19-28z receptor and is a cofounder of Juno Therapeutics, which holds the license.

pwendling@frontlinemedcom.com