car t-cell

b-cell lymphoma

hodgkin lymphoma

directors advisory committees

research funding

cell therapy

car cells

clinical trial

stem cell

Blood

Background We reported durable responses to CD19-specific chimeric antigen receptor-modified T-cell therapy (JCAR014) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients (pts) after prior failure of ibrutinib (Turtle, JCO 2017; NCT01865617). In those pts, ibrutinib was not administered during CAR-T cell immunotherapy. Continuation of ibrutinib through leukapheresis, lymphodepletion and CAR-T cell therapy may prevent tumor progression after ibrutinib withdrawal, mobilize tumor into the blood, improve CAR-T cell function, and decrease cytokine release syndrome (CRS). Methods We conducted a phase 1/2 study of CD19 CAR-T cell immunotherapy in R/R CLL pts and established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 at 2 x 106 CAR-T cells/kg (Turtle, JCO 2017). We then compared outcomes of these pts (No-ibr cohort) with a subsequent cohort that received Cy/Flu with 2 x 106/kg JCAR014 CAR-T cells with concurrent ibrutinib (420 mg/d) from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion (Ibr cohort). Dose reduction was permitted for toxicity. CRS was graded by consensus criteria (Lee, Blood 2014) and neurotoxicity and other adverse events were graded by CTCAE v4.03. Response was evaluated according to 2008 IWCLL criteria. Results Seventeen and 19 pts were treated in the Ibr and No-ibr cohorts, respectively. Pt characteristics were comparable (Table 1). Progression on ibrutinib was noted in 16 (94%) and 18 pts (95%) in the Ibr and No-ibr cohorts, respectively, and prior ibrutinib intolerance was reported in 1 pt in each cohort. The time to intolerance or failure of ibrutinib prior to treatment with JCAR014 was longer, and the pre-leukapheresis LDH was lower in the Ibr compared to the No-ibr cohort. The median follow-up in responders was 98 and 764 days in the Ibr and No-ibr cohorts, respectively. Administration of ibrutinib with Cy/Flu and JCAR014 was well tolerated in most pts; ibrutinib was reduced or discontinued in...

Comparison of Efficacy and Toxicity of CD19-Specific Chimeric Antigen Receptor T-Cells Alone or in Combination with Ibrutinib for Relapsed and/or Refractory CLL