Acute lymphoblastic leukemia relapse after CD19-targeted chimeric antigen receptor T cell therapy

Wang, Jiasheng; Hu, Yongxian; Huang, He

doi:10.1189/jlb.5ru0817-315r

Cited by 43 publications

(28 citation statements)

References 81 publications

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“…However, studies have shown that glucocorticoid treatment of CRS may reduce the efficacy of CAR-T treatment, which is a controversial finding that needs further elucidation [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

A comprehensive analysis of the fatal toxic effects associated with CD19 CAR-T cell therapy

Cai

Tang

Han

et al. 2020

Aging

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To determine the incidence, spectrum, timing, and clinical features of CD19 Chimeric antigen receptor (CAR-T) cell therapy-associated fatal toxic effects. We initiated a comprehensive analysis. First, we retrospectively queried the real-world data from a World Health Organization (WHO) pharmacovigilance database (Vigilyze). Furthermore, we performed a meta-analysis of published trials of CD19 CAR-T cell therapy. From screening the WHO database, we identified 1200 patients: 499 received Kymriah therapy, and 701 received Yescarta therapy. We compared the adverse reactions of the two drugs. We evaluated all published clinical trials, comprising 19 trials and 890 patients. Our meta-analysis showed that the incidence of fatal toxic effects associated with death was 5.4%. Infections and infestations appeared to present the highest risk of death. The toxic effect specific median time to death was 30, 30, and 68 days for total, cytokine release syndrome (CRS), and nervous system disorders (NSD), respectively. We observed a high mortality rate for some toxic effects and an early onset of death with varied causes, indicating the need for clinicians to pay more attention to the monitoring and treatment of these fatal toxic effects when using CD19 CAR-T cell therapy, especially for infections and infestations.

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“…However, studies have shown that glucocorticoid treatment of CRS may reduce the efficacy of CAR-T treatment, which is a controversial finding that needs further elucidation [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

A comprehensive analysis of the fatal toxic effects associated with CD19 CAR-T cell therapy

Cai

Tang

Han

et al. 2020

Aging

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“…Previous clinical trials showed anti‐CD19 CAR‐T therapy attained high remission rates, and caused relatively controllable adverse events in r/r B‐ALL patients . Nonetheless, due to the antigen escape of tumor cells, impaired function and reduced amount of CAR‐T cells, and the inhibitory microenvironment of bone marrow, patients who have achieved complete remission (CR) through CAR‐T therapy are still at high risk of relapse …”

Section: Introductionmentioning

confidence: 99%

Anti‐CD19 chimeric antigen receptor‐modified T‐cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B‐cell acute lymphoblastic leukemia: An open‐label pragmatic clinical trial

et al. 2019

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Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This nonrandomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD − CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD − CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD − CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

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“…Up to date, frequencies and subsequences of CD19 positive and CD19 dim or negative relapse are still unclear. [ 14 , 15 ]…”

Section: Discussionmentioning

confidence: 99%

Lymphodepletion chemotherapy revitalizes chimeric antigen receptor T cells contributing to regression of relapsed B-cell lymphoma

Liang¹,

Zhang

Shao

et al. 2020

Medicine

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Introduction: Chimeric antigen receptor T cells (CAR-T) targeting CD19 have shown great potential for treatment of B-cell malignancies. For those patients who can not achieve complete remission (CR) or suffer from relapse after CAR-T therapy, further therapeutic strategies still remain elusive. Whether existing CAR-T cells can revitalize in vivo and eradicate tumor cells is still unknown. Patient concerns: We report a case of diffused large B-cell lymphoma patient who had achieved CR after CD19 targeted CAR-T therapy but relapsed after 5 months. Diagnosis: Five months after CAR-T cell infusion, the patient was confirmed a relapse by follow-up PET/CT scan and a mass biopsy. Flow cytometry showed a dramatically decreased percentage of CAR-T cells in peripheral blood (PB). Interventions: A second anti-CD19 CAR-T therapy was planned with deliberation. Firstly, the patient received lymphodepletion chemotherapy with fludarabine (25 mg/m 2 , d1–d3) and cyclophosphamide (500 mg/m 2 d2–d3). Outcomes: After fludarabine and cyclophosphamide (FC) lymphodepletion chemotherapy, pre-existing CAR-T cells were revitalized and the patient developed grade 2 cytokine release syndrome (CRS) contributing to the regression of relapsed B-cell lymphoma. Conclusions: This case suggested that FC chemotherapy could revitalize CAR-T cells contributing to the regression of relapsed B-cell lymphoma. Nevertheless, further researches are required in the future as this report described only a single case.

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Acute lymphoblastic leukemia relapse after CD19-targeted chimeric antigen receptor T cell therapy

Cited by 43 publications

References 81 publications

A comprehensive analysis of the fatal toxic effects associated with CD19 CAR-T cell therapy

A comprehensive analysis of the fatal toxic effects associated with CD19 CAR-T cell therapy

Anti‐CD19 chimeric antigen receptor‐modified T‐cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B‐cell acute lymphoblastic leukemia: An open‐label pragmatic clinical trial

Lymphodepletion chemotherapy revitalizes chimeric antigen receptor T cells contributing to regression of relapsed B-cell lymphoma

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