Subsequent malignant neoplasms in patients previously treated with anti-CD19 CAR T-cell therapy - Research Letter

Sep 21, 2026

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Research letters address subsequent malignant neoplasms following anti-CD19 CAR T-cell therapy, focusing on rates and the incidence of secondary T-cell neoplasms. The study retrospectively analyzed 582 patients with relapsed or refractory large B-cell lymphoma treated across 13 academic centers between 2015 and 2022. Patients received a median of 3 prior therapy lines, with a median follow-up of 35.3 months and reported progression-free and overall survival estimates. Baseline features included EBV-positive disease, HIV infection, and autoimmune conditions, with attention to myeloid predominance versus other malignancies.

LanguageEnglish

CategoryHealthcare

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Pages5

Reading Time13 min

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Subsequent malignant neoplasms after anti-CD19 CAR T-cell therapy

Study rationale and background

FDA-related safety concerns for secondary neoplasms

Retrospective cohort selection and baseline characteristics

Survival outcomes and follow-up

Reporting timeline and publication details

Table 1: Baseline characteristics

RESEARCH LETTER TO THE EDITOR: Subsequent malignant neoplasms in patients previously treated with anti-CD19 CAR T-cell therapy Megan Melody, 1 Narendranath Epperla,2 Geoffrey Shouse,3 Jason Romancik,4 Pamela Allen,4 Tamara K. Moyo,5 Vaishalee Kenkre,6 Thomas Ollila,7 Lindsey Fitzgerald,8 Brian Hess,9 Kevin David, 10 Megan M. Herr, 11 Oluwatobi Odetola, 1 Adam Lin, 12 Jonathan Moreira, 12 Shuo Ma, 12 Jane N. Winter, 12 Ishan Roy, 12, 13 Deborah Stephens, 14 Alexey Danilov,3 Nirav N. Shah, 15 Stefan K. Barta, 16 Matthew Cortese, 11 Jonathon B. Cohen,4 Leo I. Gordon, 12 and Reem Karmali 12 1 Northwestern University, Feinberg School of Medicine, Chicago, IL; 2Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH; 3 City of Hope Comprehensive Cancer Center, Duarte, CA; 4Winship Cancer Institute, Emory University, Atlanta, GA; 5 Levine Cancer Institute, Atrium Health, Charlotte, NC; 6 Carbone Cancer Center, University of Wisconsin–Madison, Madison, WI; 7 Lifespan Cancer Institute, Brown University, Providence, RI; 8 Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT; 9 Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; 10 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ; 11 Roswell Park Comprehensive Cancer Center, Buffalo, NY; 12 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; 13Shirley Ryan Ability Lab, Chicago, IL; 14 Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC; 15 MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI; and 16Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA Chimeric antigen receptor (CAR) T-cell therapy is a novel therapy that uses either gamma-retroviral orlentiviral vectors to genetically modify a patient’s autologous T cells to express an anti-CD19 antibody against CD19+ B-cell malignancies.1,2 Since 2017, a total of 3 anti-CD19 CAR T-cell therapies, axicabtagene ciloleucel (axi-cel; Yescarta), tisagenlecleucel (tisa-cel; Kymriah), and lisocabtagene maraleucel (liso-cel; Breyanzi), have been approved by the FDA and have demonstrated remarkable efﬁcacyin the treatment of relapsed and refractory B-cell non-Hodgkin lymphomas (NHLs) .3-8 Initial long-term follow-up of these pivotal clinical trials showed low rates of myelodysplastic syndrome (MDS) after CAR T-cell therapy and no other subsequent malignant neoplasms (SMNs) .9, 10 However, multiple realworld retrospective analyses examining outcomes after treatment with CAR T-cell therapy report varying rates of SMNs ranging from 0 .9% to 12.9%, with the most common being MDS.8-12 These real-world studies are limited by small patient populations and often focus on the rate of treatment–related myeloid neoplasms, with limited data regarding solid tumor or other hematologic malignancies. On the 28th of November, 2023, the Food and Drug Administration (FDA) announced an investigation into reports of Tcell malignancies, including CAR-positive lymphomas, in patients who received treatment with B-cell maturation antigen (BCMA)– or CD19–directed autologous CAR T-cell immunotherapies.13, 14 These ﬁndings raise concern for an increased rate of secondary T-cell neoplasms related to potential insertionalmutagenesis from genetically modiﬁed CAR T-cell therapy.15, 16 In light of the recent announcement by the FDA of reported cases of CAR-positive T-cell lymphomas after CAR T-cell therapy, we performed a large retrospective analysis examining the rates of SMNs in patients previously treated with anti-CD19 CAR Tcell therapy, with particular attention to the incidence of T-cell neoplasms. We identiﬁed 582 patients with relapsed and refractory large B-cell lymphoma (LBCL) treated with CART-cell therapy between 2015 and 2022 across 13 academic medical centers. Patients in this cohort received a median of 3 prior l

FAQs

What question does this research letter investigate about anti-CD19 CAR T-cell therapy?

It investigates the rates of subsequent malignant neoplasms in patients previously treated with anti-CD19 CAR T-cell therapy, with particular attention to the incidence of T-cell neoplasms.

How many patients were included and what cancer type did they have?

The analysis identified 582 patients with relapsed and refractory large B-cell lymphoma treated with CAR T-cell therapy across 13 academic medical centers.

What baseline conditions were reported in the cohort?

The cohort included patients with Epstein-Barr virus (EBV)–positive disease, HIV infection, and previously diagnosed autoimmune conditions, alongside detailed CAR T-cell product distribution.

Sep 21, 2026

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