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Clinical Trial
. 2021 Dec;70(12):3501-3511.
doi: 10.1007/s00262-021-02941-4. Epub 2021 Apr 25.

CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease

Wenyi Lu  1   2 , Yunxiong Wei  1 , Yaqing Cao  1 , Xia Xiao  1   2 , Qing Li  1   2 , Hairong Lyu  1   2 , Yili Jiang  1   2 , Huan Zhang  1   2 , Xin Li  1   2 , Yanyu Jiang  1   2 , Juanxia Meng  1   2 , Ting Yuan  1   2 , Haibo Zhu  1   2 , Xiaoyuan He  2 , Xin Jin  3 , Rui Sun  1 , Tao Sui  1   2 , Kaiqi Liu  4 , Mingfeng Zhao  5   6
Affiliations
Clinical Trial

CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease

Wenyi Lu et al. Cancer Immunol Immunother. 2021 Dec.

Abstract

The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor T (CD19 CAR-T) cells have shown promising responses in B-ALL. However, their role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T cells in MRD-positive B-ALL patients. From January 2018, a total of 14 MRD-positive B-ALL patients received one or more infusions of autogenous CD19 CAR-T cells. Among them, 12 patients achieved MRD-negative remission after one cycle of CAR-T infusion. At a median follow-up time of 647 days (range 172-945 days), the 2-year event-free survival rate in MRD-positive patients was 61.2% ± 14.0% and the 2-year overall survival was 78.6 ± 11.0%, which were significantly higher than patients with active disease (blasts ≥ 5% or with extramedullary disease). Moreover, patients with MRD had a lower grade of cytokine release syndrome (CRS) than patients with active disease. However, the peak expansion of CAR-T cells in MRD positive patients showed no statistical difference compared to patients with active disease. Five patients received two or more CAR-T cell infusions and these patients showed a decreased peak expansion of CAR-T cell in subsequent infusions. In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).

Keywords: B-cell acute lymphoblastic leukemia; CD19-directed chimeric antigen receptor T cells; Cytokine release syndrome; Minimal residual disease; Relapse.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Fig. 1
Fig. 1
The probability of two-year overall survival and event-free survival in MRD-positive patients and the patients with active disease treated after CAR-T cell therapy. a The probability of two-year overall survival after CAR-T cell therapy; b The probability of two-year event-free survival after CAR-T cell therapy
Fig. 2
Fig. 2
Comparison of cytokine release and CAR-T cell proliferation between MRD-positive patients and the patients with active disease after CAR-T cell infusion. a The incidence of CRS of all grades after CAR-T cell therapy in MRD-positive B-ALL patients (n = 14) and the patients with active disease (n = 29). b–g The peak levels of serum CRP, IL-2, IL-6, IL-8, IL-10 and ferritin in MRD-positive B-ALL patients (n = 14) or the patients with active disease (n = 29); h The peak level of CD19 CAR-T cells in peripheral blood after CAR-T cell infusion
Fig. 3
Fig. 3
Proliferation of CAR-T cells after repeated infusion. a The proliferation and persistence of CAR-T cells after the second infusion; b The peak expansion of CAR-T cells after each infusion
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