Of 449 patients treated with a commercial CAR T cell product (CART) at UPenn, 16 (3.6%) were diagnosed with a secondary primary malignancy at a median follow-up of 10.3 months. This included one case of secondary T cell lymphoma (TCL), which was detected 3 months after third-line axi-cel CART-19 therapy in a patient with B-cell lymphoma, unclassifiable, in one of three lymph nodes upon surgical removal of a NSCLC lesion. The TCL harbored a JAK3 variant (unknown significance) and CD8+ cytotoxic phenotype, and was defined as negative for CAR transgene integration. Ghilardi et al. concluded that risk of TCL post CART is very low, affirming the safety of commercial CART products.
Contributed by Ute Burkhardt
ABSTRACT: We report a T-cell lymphoma (TCL) occurring three months after anti-CD19 chimeric antigen receptor (CAR) T-cell immunotherapy for non-Hodgkin B-cell lymphoma. The TCL was diagnosed from a thoracic lymph node upon surgery for lung cancer. The TCL exhibited CD8+ cytotoxic phenotype and a JAK3 variant, while the CAR transgene was very low. The T-cell clone was identified at low levels in the blood before CART infusion and in the lung cancer. To assess the overall risk of secondary primary malignancy (SPM) after commercial CART (CD19, BCMA), we analyzed 449 patients treated at the University of Pennsylvania. At a median follow-up of 10.3 months, 16 patients (3.6%) had SPM. Median onset time was 26.4 and 9.7 months for solid and hematological malignancies, respectively. The projected 5-year cumulative incidence is 15.2% for solid and 2.3% for hematological malignancies. Overall, one case of TCL was observed, suggesting a low risk of TCL post-CART.
Author Info: (1) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA,
Author Info: (1) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (2) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (3) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (4) Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Personalized Diagnostics, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (5) Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Personalized Diagnostics, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (6) Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (7) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (8) Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (9) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (10) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (11) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (12) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (13) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (14) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (15) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (16) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (17) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (18) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (19) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (20) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. (21) Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Personalized Diagnostics, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (22) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (23) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. (24) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (25) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (26) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (27) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (28) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (29) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (30) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. (31) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (32) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. (33) Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu. Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu. Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.
