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Published on: February 27, 2019
Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas
Stephen J Schuster1, Jakub Svoboda1, Elise A Chong1
1From the Lymphoma Program at the Abramson Cancer Center and the Division of Hematology-Oncology (S.J.S., J.S., E.A.C., S.D.N., A.R.M., D.L., D.L.P.), and the Department of Pathology and Laboratory Medicine (V.B., M.W., B.L.L., S.F.L., J.J.M., C.H.J.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Novartis Pharmaceuticals, Basel, Switzerland (Ö.A.); and Novartis Institutes for BioMedical Research, Cambridge, MA (J.L.B., I.P-M.).
Chimeric antigen receptor (CAR) T cells targeting CD19 show promise for treating refractory B-cell lymphomas. This study found high durable remission rates in diffuse large B-cell lymphoma and follicular lymphoma patients, despite manageable toxicities.
Area of Science:
- Oncology
- Immunotherapy
- Hematology
Background:
- Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) refractory to standard treatments have poor prognoses.
- Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown high response rates in B-cell cancers, but data in lymphomas are limited.
Purpose of the Study:
- To evaluate the efficacy and safety of CD19-directed CAR T cells (CTL019) in adult patients with relapsed or refractory DLBCL or FL.
- To assess treatment response, toxic effects, CTL019 cell kinetics, and immune recovery.
Main Methods:
- Autologous T cells engineered to express a CD19-directed CAR (CTL019) were administered to 28 adult patients with relapsed/refractory DLBCL or FL.
- Patients were monitored for clinical response, adverse events, CAR T-cell expansion and persistence, and immune reconstitution.
Main Results:
- Overall response rate was 64% (18/28 patients). Complete remission (CR) was achieved in 43% of DLBCL patients and 71% of FL patients.
- Durable remissions were observed, with 86% of DLBCL responders and 89% of FL responders maintaining response at a median follow-up of 28.6 months.
- Severe cytokine-release syndrome occurred in 18% of patients, and serious encephalopathy in 11%, with one fatal case.
Conclusions:
- CTL019 CAR T-cell therapy is effective for treating relapsed or refractory DLBCL and FL, yielding high durable remission rates.
- While significant toxicities like cytokine-release syndrome and encephalopathy were observed, B-cell and immunoglobulin recovery occurred in some patients.
- The study highlights the potential of CAR T-cell therapy for aggressive B-cell lymphomas, necessitating careful management of associated toxicities.
