Phase IIa trial of chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas.

8516 Background: Autologous T cells expressing a chimeric antigen receptor with an external anti-CD19 single chain antibody domain and CD3ζ and 4-1BB signaling domains (CTL019 cells) mediate anti-tumor effects in patients (pts) with relapsed/refractory (r/r) CD19+ leukemias. We are conducting a phase IIa clinical trial of CTL019 cells in r/r CD19+ non-Hodgkin lymphomas. Methods: Eligible pts have CD19+ follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), or mantle cell lymphoma (MCL) with anticipated survival less than 2 years. After collection of peripheral blood leukocytes, pts receive lymphodepleting chemotherapy based on histology and past therapies. One to 4 days after chemotherapy, pts receive 5 x 108CTL019 cells intravenously. Blood and marrow samples are collected for correlative studies. Response assessment is 3 months (mo) after infusion. Enrollment began February 2014; data reported are through January 2015. Results: Twenty-nine pts (19 DLBCL; 8 FL; 2 MCL) have enrolled. Median age is 56 (range: 25-77), male:female ratio 17:12, median prior therapies 4 (range: 1-8), and pts with prior ASCT 9 (31%). At enrollment, stages were: IV, 16 pts (55%); III, 5 pts (17%); II, 6 pts (21%); IE, 2 pts (7%); LDH was increased in 20 pts (69%). Eight pts are not evaluable for response (DLBCL 7; FL 1): 3 pts removed from study before T cell infusion due to progressive disease; 1 pt withdrew consent; 3 pts had inadequate T cell expansion; 1 pt received < protocol-specified cell dose. Twenty pts received CTL019 per protocol dose (12 DLBCL; 7 FL; 1 MCL). Pre-infusion chemotherapy regimens were EPOCH (2); cyclophosphamide (9); radiation + cyclophosphamide (2); bendamustine (6); cyclophosphamide-fludarabine (1). Cytokine release syndrome occurred in 15 pts (13 grade 2; 2 grade 3); neurologic toxicity in 3 pts: transient delirium (1 grade 2, 1 grade 3) and 1 possibly related, grade 5 encephalopathy. For 18 pts evaluable for response at 3 mo (12 DLBCL; 6 FL), overall response rate is 67% (DLBCL 50%; FL 100%). At median follow up 6 mo, progression-free survival for evaluable pts is 59% (DLBCL 37%; FL 100%). Conclusions: CTL019 cells induce durable responses in pts with r/r DLBCL and FL with acceptable toxicity. Clinical trial information: NCT02030834.