T-Cell Lymphoma Following CAR T-Cell Therapy

Cellular immunotherapy with chimeric antigen receptor (CAR) T-cell products can provide durable responses in relapsed and refractory B-cell malignancies, but rare cases of T-cell malignancy among patients treated with CAR T have been identified. Two research groups examine this issue.

To assess the risk of second primary malignancies in recipients of CAR-T therapy, investigators with partial industry support conducted a single-institution retrospective analysis. Since 2016, the study cohort was comprised of 724 unique patients who underwent 791 therapeutic CAR-T infusions. A single case of a T-cell lymphoma positive for Epstein-Barr virus was identified in a 59-year-old woman previously treated with CAR T-cell therapy (axicabtagene ciloleucel) for relapsed diffuse large B-cell lymphoma. Detailed molecular analysis showed that the two lymphomas were distinct, although a pre-existing T-cell clonal population was found in blood samples obtained prior to CAR T administration. The T-cell lymphoma was not derived from the CAR T-cell population itself; additionally, CAR T retroviral vector integration was not identified in the T-cell lymphoma.

In another case report, a patient with myeloma treated with ciltacabtagene autoleucel (age, 71) was later diagnosed with indolent T-cell lymphoma. Here, lentiviral insertion in tumor DNA was found in addition to other potentially transforming mutations.