[HTML][HTML] Autologous CD19-targeted CAR T cells in patients with residual CLL following initial purine analog-based therapy

MB Geyer, I Rivière, B Sénéchal, X Wang, Y Wang… - Molecular Therapy, 2018 - cell.com
MB Geyer, I Rivière, B Sénéchal, X Wang, Y Wang, TJ Purdon, M Hsu, SM Devlin, E Halton…
Molecular Therapy, 2018cell.com
Patients with residual chronic lymphocytic leukemia (CLL) following initial purine analog-
based chemoimmunotherapy exhibit a shorter duration of response and may benefit from
novel therapeutic strategies. We and others have previously described the safety and
efficacy of autologous T cells modified to express anti-CD19 chimeric antigen receptors
(CARs) in patients with relapsed or refractory B cell acute lymphoblastic leukemia and CLL.
Here we report the use of CD19-targeted CAR T cells incorporating the intracellular …
Patients with residual chronic lymphocytic leukemia (CLL) following initial purine analog-based chemoimmunotherapy exhibit a shorter duration of response and may benefit from novel therapeutic strategies. We and others have previously described the safety and efficacy of autologous T cells modified to express anti-CD19 chimeric antigen receptors (CARs) in patients with relapsed or refractory B cell acute lymphoblastic leukemia and CLL. Here we report the use of CD19-targeted CAR T cells incorporating the intracellular signaling domain of CD28 (19-28z) as a consolidative therapy in 8 patients with residual CLL following first-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab. Outpatients received low-dose conditioning therapy with cyclophosphamide (600 mg/m2), followed by escalating doses of 3 × 106, 1 × 107, or 3 × 107 19-28z CAR T cells/kg. An objective response was observed in 3 of 8 patients (38%), with a clinically complete response lasting more than 28 months observed in two patients. Self-limited fevers were observed post-CAR T cell infusion in 4 patients, contemporaneous with elevations in interleukin-6 (IL-6), IL-10, IL-2, and TGF-α. None developed severe cytokine release syndrome or neurotoxicity. CAR T cells were detectable post-infusion in 4 patients, with a longest observed persistence of 48 days by qPCR. Further strategies to enhance CAR T cell efficacy in CLL are under investigation.
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