Targeted Therapy Brings Remission in Patient With CAR-Positive T-Cell Lymphoma

A 51-year-old patient who developed chimeric antigen receptor (CAR)-positive T-cell lymphoma was successfully treated with targeted therapy, according to a case report published in The New England Journal of Medicine. The treatment marks the first reported case of using targeted therapy in this way.¹

CAR T-cell therapy injected into tumor cell 3D visualization | Image Credit: © john - stock.adobe.com

"This is the first reported case of successfully using targeted therapy to treat a CAR-positive T-cell lymphoma," Samir Parekh, MD, of the Icahn School of Medicine at Mount Sinai in New York City, said in a news release. "It highlights the importance of monitoring for secondary cancers and leveraging precision medicine to respond quickly when they emerge."²

Secondary malignancies following CAR T-cell therapy are rare, albeit a severe adverse effect—one that warranted mandated Black Box warnings on all approved CAR products by the FDA in 2023. This came in response to more than 20 instances of second cancers, specifically T-cell lymphoma. The patient in this case report was initially treated with ciltacabtagene autoleucel (Carvykti; Janssen Biotech, Inc) for multiple myeloma (MM), which led to his initial remission. However, 6 months later, he developed erythematous facial lesions and lymphocytosis.^2,3

Biopsies of the skin and bone marrow confirmed the patient developed CAR-positive T-cell lymphoma. Using single-cell RNA and T-cell receptor sequencing, Parekh’s team identified a high expression of CCR4—an indicator of poor outcomes that is rarely upregulated in peripheral T-cell lymphoma. Following an assay used to identify which FDA-approved drugs would be safe and efficacious, they decided on mogamulizumab (Poteligeo; Kyowa Kirin), an anti-CCR4 antibody. They also included liposomal doxorubicin and gemcitabine.²

The treatment proved successful; within a few days of treatment, there were noticeable improvements in the patient’s skin lesions and a reduction in white blood cell counts. Notably, the patient achieved complete remission for both his MM and lymphoma.²

Parekh and their team reported another key finding from the patient’s case. They found that the lymphoma emerged from clone T-cells harboring a TET2 mutation.²

"This mutation can exist at low levels in older individuals and be innocuous, or in some cases, lead to pre-leukemia, or even contribute to leukemia," he explained. "And it has been shown to be involved in the pathogenesis of T-cell lymphoma. Clearly in this case, the clone was at a low level and went to a much higher level and was actually involved in the tumor."²

Despite the prevalence of TET2 patients with MM receiving CAR T-cell therapy—approximately half of all patients—many are not screened for this mutation. Parekh’s team suggest pharmacists and care teams screen for clonal hematopoiesis prior to CAR T-cell therapy with monitoring after treatment to identify patients with a high-risk of developing secondary malignancies.

REFERENCES

1. Aleman A, Van Oekelen O, Melnekoff D, et al. Targeted therapy of CAR+ T-cell lymphoma after anti-BCMA CAR T-cell therapy. N Engl Med. August 20, 2025. doi: 10.1056/NEJMc2504588

2. Bassett M. treatment succeeds for secondary cancer after CAR-T, case report shows. MedPage Today. August 22, 2025. Accessed August 25, 2025. https://www.medpagetoday.com/hematologyoncology/hematology/117130

3. Phillips C. Understanding the risk of second cancers after CAR T-cell therapy. National Cancer Institute. August 13, 2024. Accessed August 25, 2025. https://www.cancer.gov/news-events/cancer-currents-blog/2024/car-t-cell-therapy-second-cancers