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

Sep 23, 2026

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Chimeric antigen receptor T-cell (CAR-T) therapy improves outcomes for relapsed/refractory hematologic malignancies, but long-term complications remain insufficiently characterized. A retrospective cohort of 246 adults treated with CAR-T at Ohio State University between 2016 and 2022 (minimum 2 years follow-up) identified second primary malignancies (SPM) in 21 patients (8.5%). Non-melanoma skin cancer was most common (52%), followed by hematologic malignancies (33%) and non-skin solid tumors (14%). The observed SPM pattern suggests potential CAR-T-related risks, supporting vigilant post-treatment surveillance and further studies to clarify mechanisms and predictors.

LanguageEnglish

CategoryHealthcare

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Pages3

Reading Time8 min

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Abstract

Correspondence

Retrospective analysis and patient characteristics

CAR-T products and timing of SPM diagnosis

Distribution of second primary malignancies

Umyarova et al. Journal of Hematology & Oncology (2025) 18:30 [https://doi.org/10.1186/s13045-025-01676-4](https://doi.org/10.1186/s13045-025-01676-4) Journal of Hematology & Oncology CORRESPONDENCE Open Access Second primary malignancies following CAR T-cell therapy in patients with hematologic malignancies Elvira Umyarova1*, Charles Pei1, William Pellegrino1, Qiuhong Zhao1, Nidhi Sharma1, Don Benson 1, Francesca Cottini1, Evandro Bezerra 1, Jonathan Brammer 1, Naresh Bumma 1, Hannah Choe1, Nathan Denlinger 1, Srinivas Devarakonda1, Abdullah Khan1, Sam Penza1, Ashley Rosko1, Sumithira Vasu1, Sarah Wall1, Lapo Alinari1, Robert Baiocchi1, David A. Bond 1, Beth Christian1, Walter Hanel1, Kami Maddocks 1, John Reneau1, Yazeed Sawalha1, Alma Habib1, Audrey Sigmund1, Timothy J. Voorhees 1, Marcos de Lima 1 and Narendranath Epperla 1,2* 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 Second primary malignancies, SPM, CAR-T, LBCL, MM *Correspondence: Elvira Umyarova [Elvira.Umyarova@osumc.edu](Elvira.Umyarova@osumc.edu)[ ](Elvira.Umyarova@osumc.edu)Narendranath Epperla [naren.epperla@hci.utah.edu](naren.epperla@hci.utah.edu) 1 Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA 2 Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84103, USA To the Editor, Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory (R/R) hematologic malignancies, including B-cell acute lymphoblastic leukemia, B-cell lymphomas, and multiple myeloma (MM). The durable remissions associated with CAR-T in these challenging cases have established it as a transformative option for patients with limited © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or

FAQs

How many patients developed a second primary malignancy (SPM) after CAR-T therapy, and what was the overall incidence?

Among 246 treated patients, 21 developed an SPM, giving an incidence of 8.5%.

Which type of SPM was the most common in this cohort?

Non-melanoma skin cancer was the most common SPM, occurring in 52% of the cases.

What was the study design and follow-up duration used to assess long-term SPM risk?

The analysis retrospectively included adults treated with CAR-T between 2016 and 2022 at Ohio State University with a minimum of two years of post-CAR-T follow-up; median follow-up was 38 months (range 11–66).

Sep 23, 2026

Uploaded by Miles