JCAR014 is a CD19-specific chimeric antigen receptor (CAR)-modified T-cell therapy developed by Juno Therapeutics. Previous research has shown durable responses in relapsed/refractory chronic lymphocytic leukemia (CLL) after failure with ibrutinib. In those studies, ibrutinib was not administered during CAR-T cell therapy. A group of researchers recently evaluated whether continuation of ibrutinib through leukapheresis, lymphodepletion, and CAR T-cell therapy would prevent tumor progression after ibrutinib withdrawal, improve CAR-T cell function, and decrease cytokine release syndrome (CRS).
Their results, presented at the ASH annual meeting, demonstrated that the approach was well tolerated in most patients and “might decrease the incidence of severe CRS and improve responses in patients with relapsed/refractory CLL,” according to lead author Jordan Gauthier, MD, Fred Hutchinson Cancer Research Center.
The phase I/II study used a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 in one cohort. The researchers compared outcomes with a second cohort of patients who received Cy/Flu, JCAR014, and concurrent ibrutinib from at least two weeks prior to leukapheresis until at least three months after JCAR014 infusion. The ibrutinib had a higher proportion of responders (complete or partial remission)—88% versus 56%.
Ibrutinib with Cy/Flu and JCAR014 was well tolerated in most patients, but ibrutinib was reduced or discontinued in six patients (35%) a median of 21 days after JCAR014 infusion. In the ibrutinib group, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia. The groups did not differ in incidence of grade 3 or higher cytopenia, or frequency or severity of neurotoxicity. Incidence of grade 1 or higher CRS also was similar between groups, but the severity of CRS was lower in the ibrutinib cohort.