Sang Yun Lee

No chimeric antigen receptor therapy (CAR-T) is currently approved for WM. This study assessed safety and efficacy of CD20-targeted CAR-T in BTKi-refractory, heavily pre-treated WM patients. With a CR/VGPR rate of 80%, this treatment should be evaluated in larger trials. ClinicalTrials.gov number NCT03277729

Table S4. Staining panel used for multiplex immunohistochemistry

Table S1. Baseline cytokine levels (prior to lymphodepletion) for UPN-03 and UPN-04.

Figure S1. Cellular composition of the post-treatment tumor biopsy of patient UPN-03. Figure S2. Gating strategy for multiparameter flow cytometry for UPN-03. Figure S3. Gating strategy for multiparameter flow cytometry for UPN-04.

Table S2. Differentially expressed TCR-β CDR3 sequences increased at 3 and/or 35 month timepoints in patient UPN-04

Table S3. Cellular composition of post-infusion timepoints.

Chimeric antigen receptor (CAR) T-cell therapy produces high response rates in refractory B-cell non–Hodgkin lymphoma, but long-term data are minimal to date. In this study, we present long-term follow-up of a pilot trial testing a CD20-targeting third-generation CAR in patients with relapsed B-cell lymphomas following cyclophosphamide-only lymphodepletion. Two of the three 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-term remissions. Correlative immunologic analyses supported this hypothesis, with evidence of new humoral and cellular antitumor 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.Significance:Two of three patients treated with CD20-targeted CAR T-cell therapy had long-term remissions, with evidence of endogenous antitumor immune response formation. Further investigation is warranted to develop conditions that promote epitope spreading in lymphomas.

Table S2. Differentially expressed TCR-β CDR3 sequences increased at 3 and/or 35 month timepoints in patient UPN-04

Table S1. Baseline cytokine levels (prior to lymphodepletion) for UPN-03 and UPN-04.

Table S4. Staining panel used for multiplex immunohistochemistry