Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 18;18(1):30.
doi: 10.1186/s13045-025-01676-4.

Second primary malignancies following CAR T-cell therapy in patients with hematologic malignancies

Elvira Umyarova  1 , Charles Pei  2 , William Pellegrino  2 , Qiuhong Zhao  2 , Nidhi Sharma  2 , Don Benson  2 , Francesca Cottini  2 , Evandro Bezerra  2 , Jonathan Brammer  2 , Naresh Bumma  2 , Hannah Choe  2 , Nathan Denlinger  2 , Srinivas Devarakonda  2 , Abdullah Khan  2 , Sam Penza  2 , Ashley Rosko  2 , Sumithira Vasu  2 , Sarah Wall  2 , Lapo Alinari  2 , Robert Baiocchi  2 , David A Bond  2 , Beth Christian  2 , Walter Hanel  2 , Kami Maddocks  2 , John Reneau  2 , Yazeed Sawalha  2 , Alma Habib  2 , Audrey Sigmund  2 , Timothy J Voorhees  2 , Marcos de Lima  2 , Narendranath Epperla  3   4
Affiliations

Second primary malignancies following CAR T-cell therapy in patients with hematologic malignancies

Elvira Umyarova et al. J Hematol Oncol. .

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of patients with relapsed/refractory (R/R) hematologic malignancies, including B-cell lymphomas and multiple myeloma (MM). While data pertaining to the efficacy and toxicity associated with CAR-T have been widely reported, there are limited data on long-term complications. We retrospectively analyzed 246 patients treated with CAR-T for R/R B-cell lymphoma (n = 228) and MM (n = 18) at Ohio State University from 2016 to 2022, with a minimum of two years of follow-up. The median age was 66 years, and the median number of prior treatments was four. With a median follow-up of 38 months (range 11-66), 21 patients (8.5%) developed a second primary malignancy (SPM), with non-melanoma skin cancer being the most common (52%), followed by hematologic malignancies (33%) and non-skin solid tumors (14%). Squamous cell carcinoma accounted for 38% of skin cancers, while myelodysplastic syndrome and acute myeloid leukemia were the predominant hematologic malignancies. Solid tumors included bladder, prostate, and breast cancer. The distinct pattern of SPMs suggests potential CAR-T-related risks, warranting vigilant post-treatment surveillance. Further studies are necessary to elucidate underlying mechanism and predictive factors and guide long-term management of SPM risk in CAR-T survivors.

Keywords: CAR-T; LBCL; MM; SPM; Second primary malignancies.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate : The study was approved by the institutional review board at OSU and was conducted in compliance with the Declaration of Helsinki. Competing interests: The authors declare no competing interests.

References

    1. Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023;20(6):359–71. - PMC - PubMed
    1. Verdun N, Marks P. Secondary cancers after chimeric antigen receptor T-cell therapy. N Engl J Med. 2024;390(7):584–6. - PubMed
    1. Elsallab M, Ellithi M, Lunning MA, et al. Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA adverse events reporting system. Blood. 2024;143(20):2099–105. - PubMed
    1. Shen J, Hu R, Lin A, et al. Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase. EClinicalMedicine. 2024;73: 102684. - PMC - PubMed
    1. Tix T, Alhomoud M, Shouval R, et al. Second primary malignancies after CAR T-cell therapy: A systematic review and meta-analysis of 5,517 lymphoma and myeloma patients. Clin Cancer Res. 2024;30(20):4690–700. - PMC - PubMed

Substances