Long-term Remissions Following CD20-directed Chimeric Antigen Receptor Adoptive T cell Therapy.
George MoSang-Yun LeeDavid G CoffeyValentin VoilletIlan R KirschRaphaël GottardoKimberly S SmytheCecilia C S YeungAdam GreenbaumDamian J GreenDavid G MaloneyBrian G TillPublished in: Blood cancer discovery (2024)
Chimeric antigen receptor (CAR) T cell therapy produces high response rates in refractory B-cell non-Hodgkin lymphoma (NHL), but long-term data are minimal to date. Here, we present long-term follow-up of a pilot trial testing a CD20-targeting 3rd generation CAR in patients with relapsed B-cell lymphomas following cyclophosphamide-only lymphodepletion. Two of the 3 patients in the trial, with mantle cell lymphoma and follicular lymphoma, had remissions lasting more than 7 years, though they ultimately relapsed. The absence of B cell aplasia in both patients suggested a lack of functional CAR T cell persistence, leading to the hypothesis that endogenous immune responses were responsible for these long remissions. Correlative immunologic analyses supported this hypothesis, with evidence of new humoral and cellular anti-tumor immune responses proximal to clinical response time points. Collectively, our results suggest that CAR T cell therapy may facilitate epitope spreading and endogenous immune response formation in lymphomas.
Keyphrases
- cell therapy
- immune response
- stem cells
- end stage renal disease
- mesenchymal stem cells
- chronic kidney disease
- newly diagnosed
- ejection fraction
- acute lymphoblastic leukemia
- dendritic cells
- prognostic factors
- clinical trial
- low dose
- drug delivery
- high dose
- multiple myeloma
- cancer therapy
- inflammatory response
- nk cells
- phase ii