Publications by authors named "Eugenio Fardella"

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31).

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CD19-directed chimeric antigen receptor (CAR) T cells can induce durable remissions in relapsed/refractory large B-cell lymphomas (R/R LBCLs), but 60% of patients do not respond or relapse. Biological mechanisms explaining lack of response are emerging, but they are largely unsuccessful in predicting disease response at the patient level. Additionally, to maximize the cost-effectiveness of CAR T-cell therapy, biomarkers able to predict response and survival before CAR T-cell manufacturing would be desirable.

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Article Synopsis
  • A T cell lymphoma (TCL) case was reported occurring three months after a patient received anti-CD19 CAR T cell therapy for non-Hodgkin B cell lymphoma, diagnosed through surgery for lung cancer.
  • The TCL showed a CD8 cytotoxic profile and a JAK3 variant, and it was identified at low levels prior to CAR T infusion and also in the lung cancer samples.
  • An analysis of 449 patients treated with CAR T therapy revealed that 3.6% developed a secondary primary malignancy, with a low overall risk of TCL after such treatment.
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Purpose: In clinical trials, the expansion and persistence of chimeric antigen receptor (CAR) T cells correlate with therapeutic efficacy. However, properties of CAR T cells that enable their in vivo proliferation have still to be consistently defined and the role of CAR T bag content has never been investigated in a real-life setting.

Experimental Design: Residual cells obtained after washing 61 anti-CD19 CAR T product bags were analyzed to identify tisagenlecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features associated with postinfusion CAR T-cell in vivo expansion and with response and survival.

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