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. 2023 Mar 16;24(6):5688.
doi: 10.3390/ijms24065688.

CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma

Valerie Wittibschlager  1 , Ulrike Bacher  2 , Katja Seipel  1 , Naomi Porret  2 , Gertrud Wiedemann  2 , Claudia Haslebacher  1 , Michèle Hoffmann  1 , Michael Daskalakis  2 , Dilara Akhoundova  1 , Thomas Pabst  1   3
Affiliations

CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma

Valerie Wittibschlager et al. Int J Mol Sci. .

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to investigate the correlation between CAR T-cell persistence in the peripheral blood (PB) at 6 months, assessed by droplet digital PCR (ddPCR), with CAR T-cell treatment outcome. 92 patients with r/r B-cell lymphomas were treated with CD19-targeting CAR T-cell therapies at our institution between 01/2019-08/2022. Six months post-treatment, 15 (16%) patients had no detectable circulating CAR-T constructs by ddPCR. Patients with CAR T-cell persistence had a significantly higher CAR T-cell peak (5432 vs. 620 copies/ug cfDNA, p = 0.0096), as well as higher incidence of immune effector cell-associated neurotoxicity syndrome (37% vs. 7%, p = 0.0182). After a median follow-up of 8.5 months, 31 (34%) patients relapsed. Lymphoma relapses were less frequent among patients with CAR T-cell persistence (29% vs. 60%, p = 0.0336), and CAR T-cell persistence in the PB at 6 months was associated with longer progression-free survival (PFS) (HR 2.79, 95% CI: 1.09-7.11, p = 0.0319). Moreover, we observed a trend towards improved overall survival (OS) (HR 1.99, 95% CI: 0.68-5.82, p = 0.2092) for these patients. In our cohort of 92 B-cell lymphomas, CAR T-cell persistence at 6 months was associated with lower relapse rates and longer PFS. Moreover, our data confirm that 4-1BB-CAR T-cells have a longer persistence as compared to CD-28-based CAR T-cells.

Keywords: B-cell lymphoma; CAR T-cell persistence; CAR T-cell therapy; ddPCR.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CAR T-cell dynamics in the PB in patients included in the study: (A) in the entire patient cohort; (B) in patients treated with Kymriah®; (C) in patients treated with Yescarta®/Tecartus®; (D) Comparison of moving average plots from A, B and C. Violet: average line for all patients; blue: average line for patients treated with Kymriah®; green: average line for patients treated with Yescarta®/Tecartus®.
Figure 2
Figure 2
CAR-T cell construct concentrations in the PB at 1, 3, 6, 12, 18, 24, 30 and 36 months post-treatment. (A) in the entire patient cohort; (B) in patients treated with Kymriah®; (C) in patients treated with Yescarta®/Tecartus®; (D) comparison between the Kymriah® vs. Yescarta®/Tecartus® cohorts; (E) Comparison of CAR T-cell peak levels between all patients vs. Kymriah® cohort vs. Yesarta®/Tecartus® cohort; Grey dashed line: Quartiles; Black dashed line: Median; Abbreviations: K: Kymriah®; Mo: month(s); T: Tecartus®; Y: Yescarta®. Black: all patients; blue: patients treated with Kymriah®; green: patients treated with Yescarta®/Tecartus®.
Figure 3
Figure 3
Clinical outcomes in patients with detectable vs. non-detectable CAR T-cells by ddPCR in the PB at 6 months post-CAR T-cell treatment (A) PFS in the entire cohort; (B) OS in the entire cohort; (C) PFS in patients treated with Kymriah®; (D) OS in patients treated with Kymriah®; (E) PFS in patients treated with Yescarta®/Tecartus®; (F) OS in patients treated with Yescarta®/Tecartus®. Abbreviations: OS: overall survival: PFS: progression-free survival. Orange: patients with negative ddPCR for CAR-T constructs in PB at 6 months; pink: patients with positive ddPCR for CAR-T constructs in PB at 6 months.
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