T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy

Guido Ghilardi; Joseph A Fraietta; James N Gerson; Vivianna M Van Deerlin; Jennifer J D Morrissette; Gabriel C Caponetti; Luca Paruzzo; Jaryse C Harris; Elise A Chong; Sandra P Susanibar Adaniya; Jakub Svoboda; Sunita D Nasta; Ositadimma H Ugwuanyi; Daniel J Landsburg; Eugenio Fardella; Adam J Waxman; Emeline R Chong; Vrutti Patel; Raymone Pajarillo; Irina Kulikovskaya; David B Lieberman; Adam D Cohen; Bruce L Levine; Edward A Stadtmauer; Noelle V Frey; Dan T Vogl; Elizabeth O Hexner; Stefan K Barta; David L Porter; Alfred L Garfall; Stephen J Schuster; Carl H June; Marco Ruella

doi:10.1038/s41591-024-02826-w

T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy

Nat Med. 2024 Apr;30(4):984-989. doi: 10.1038/s41591-024-02826-w. Epub 2024 Jan 24.

Authors

Guido Ghilardi^{1

2

3}, Joseph A Fraietta^{2

4}, James N Gerson^{1

3}, Vivianna M Van Deerlin^{5

6}, Jennifer J D Morrissette^{5

6}, Gabriel C Caponetti⁵, Luca Paruzzo^{1

2

3}, Jaryse C Harris⁵, Elise A Chong^{1

2

3}, Sandra P Susanibar Adaniya^{2

3

4}, Jakub Svoboda^{1

2

3}, Sunita D Nasta^{1

2

3}, Ositadimma H Ugwuanyi^{1

2

3}, Daniel J Landsburg^{1

3}, Eugenio Fardella^{1

2

3}, Adam J Waxman^{2

3

4}, Emeline R Chong^{1

2

3}, Vrutti Patel^{1

2

3}, Raymone Pajarillo^{1

2

3}, Irina Kulikovskaya², David B Lieberman^{5

6}, Adam D Cohen^{2

3

4}, Bruce L Levine², Edward A Stadtmauer^{2

3

4}, Noelle V Frey^{2

3

4}, Dan T Vogl^{2

3

4}, Elizabeth O Hexner^{2

3

4}, Stefan K Barta^{1

2

3}, David L Porter^{2

3

4}, Alfred L Garfall^{2

3

4}, Stephen J Schuster^{1

2

3}, Carl H June², Marco Ruella^{7

8

9

10

11}

Affiliations

¹ Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
² Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
³ Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁴ Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁶ Center for Personalized Diagnostics, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁷ Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.
⁸ Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.
⁹ Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.
¹⁰ Center for Cell Therapy and Transplant, University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.
¹¹ Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. mruella@upenn.edu.

PMID: 38266761
DOI: 10.1038/s41591-024-02826-w

Abstract

We report a T cell lymphoma (TCL) occurring 3 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 CAR T infusion and in lung cancer. To assess the overall risk of secondary primary malignancy after commercial CAR T (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 a secondary primary malignancy. The 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 after CAR T.

MeSH terms

Antigens, CD19
Hematologic Neoplasms*
Humans
Immunotherapy, Adoptive / adverse effects
Lung Neoplasms*
Lymphoma, B-Cell*
Lymphoma, T-Cell*
Receptors, Antigen, T-Cell / genetics
Receptors, Chimeric Antigen* / genetics

Substances

Receptors, Chimeric Antigen
Receptors, Antigen, T-Cell
Antigens, CD19

Abstract

MeSH terms

Substances

Grants and funding