Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

Zhang, Huanxin; Zhang, Yan; Wang, Ying; Qi, Yuekun; Hu, Yongxian; Li, Ping; Cao, Jiang; Zhang, Meng; Xiao, Xia; Shi, Ming; Xia, Jieyun; Ma, Sha; Qiao, Jianlin; Li, Hujun; Pan, Bin; Qi, Kunming; Cheng, Hai; Sun, Haiying; Zhu, Feng; Sang, Wei; Li, Depeng; Li, Zhenyu; Zheng, Junnian; Zhao, Mingfeng; Liang, Aibin; Huang, He; Xu, Kailin

doi:10.3389/fimmu.2022.965224

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…The included studies were published between 2019 and 2023 and deemed relatively high quality ( Table 1 ). The meta-analysis analyzed the sustained efficacy of CAR T-cell therapy for a total of 69 patients with CNSL, who achieved an objective response [complete response (CR) or partial response (PR)], across 12 cohort studies ( Frigault et al, 2019 ; Li et al, 2020 ; Ahmed et al, 2021 ; Ghafouri et al, 2021 ; Roddie et al, 2021 ; Siddiqi et al, 2021 ; Wu et al, 2021 ; Frigault et al, 2022 ; Liu et al, 2022 ; Xue et al, 2022 ; Zhang et al, 2022 ; Lacan et al, 2023 ). These studies encompassed 27 PCNSL and 42 SCNSL, with sample sizes ranging from 2 to 14.…”

Section: Resultsmentioning

confidence: 99%

“…These studies encompassed 27 PCNSL and 42 SCNSL, with sample sizes ranging from 2 to 14. Patients underwent CAR T-cell monotherapy in six studies ( Frigault et al, 2019 ; Ahmed et al, 2021 ; Ghafouri et al, 2021 ; Roddie et al, 2021 ; Frigault et al, 2022 ; Zhang et al, 2022 ) and ASCT combined with CAR T-cell therapy in one study ( Wu et al, 2021 ), while diverse treatments containing CAR T-cell therapy were employed in the remaining five studies ( Li et al, 2020 ; Siddiqi et al, 2021 ; Liu et al, 2022 ; Xue et al, 2022 ; Lacan et al, 2023 ). For co-stimulation domains, two studies used CD28 ( Ghafouri et al, 2021 ; Siddiqi et al, 2021 ), six studies used 4-1BB ( Frigault et al, 2019 ; Roddie et al, 2021 ; Frigault et al, 2022 ; Liu et al, 2022 ; Xue et al, 2022 ; Zhang et al, 2022 ), two studies contained both CD28 and 4-1BB ( Ahmed et al, 2021 ; Lacan et al, 2023 ), and two studies used CD28/4-1BB ( Li et al, 2020 ; Wu et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data

Zhou,

Wang,

Wang

et al. 2024

Front. Pharmacol.

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Background: Central nervous system lymphoma (CNSL) is considered an aggressive lymphoma with a poor prognosis. Studies investigating CNSL have shown that chimeric antigen receptor (CAR) T-cell therapy has demonstrated an effective response in limited sample sizes. Therefore, we conducted this systematic review and meta-analysis to clarify the sustained efficacy and factors associated with the sustained efficacy of CAR T-cell therapy in the treatment of CNSL.Methods: We searched studies from PubMed, Embase, Medline, and the Cochrane Center Register of Controlled Trials up to July 2023. Studies that included individual data on the duration of response (DoR) after receiving CAR T-cell therapy were enrolled. Pooled response rates were calculated using fixed-effects or random-effects models. Subgroup analysis was performed to analyze the heterogeneity, and a Cox regression model was performed to identify the factors associated with sustained efficacy.Results: In total, 12 studies including 69 patients were identified and included in this meta-analysis. The pooled relapse rate was 45% [95% CI 35, 56]. Subgroup analyses of relapse rates revealed that CAR T-cells using the CD28/4-1BB domain (CD28/4-1BB vs. CD28 vs. 4-1BB, p = 0.0151), parenchymal or leptomeningeal involvement (parenchymal or leptomeningeal vs. both parenchymal and leptomeningeal, p < 0.0001), and combined treatment with CAR T-cell therapy [Autologous stem cell transplantation (ASCT) plus CAR T-cell therapy vs. CAR T cells with maintenance therapy vs. CAR T-cell therapy alone, p = 0.003] were associated with lower relapse rates in patients. Time-to-event endpoints were assessed using reconstructed individual patient survival data to explore key modulators of DoR. Partial response status at CAR-T infusion and the use of ASCT plus CAR T-cell therapy were associated with longer DoR at the multivariate level, with hazard ratios of 0.25 and 0.26, respectively.Conclusion: CAR T-cell therapy shows promising and sustained efficacy in CNSL patients. However, further prospective large-scale studies are needed to assess these effect modifiers to optimize patient selection and improve the sustained efficacy of CAR T-cell therapy in the treatment of CNSL.Systematic review registration:https://clinicaltrials.gov/, identifier PROSPERO CRD42023451856.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data

Zhou,

Wang,

Wang

et al. 2024

Front. Pharmacol.

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“… 8 Several case studies have reported the efficacy and manageable adverse events of CAR-T therapy in primary and SCNSL, however in small, mostly single center cohorts and with short follow-up. 9 , 10 , 11 , 12 , 13 , 14 Duration of remission of SCNSL after CD19 CAR-T therapy has also been suggested to be shorter than that for patients without CNS involvement, 11 highlighting the need for longer follow-up.…”

mentioning

confidence: 99%

Real-world results of CAR T-cell therapy for large B-cell lymphoma with CNS involvement: a GLA/DRST study

Ayuk¹,

Gagelmann

Tresckow

et al. 2023

Blood Advances

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Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia

Zhao,

Bai,

Guo

et al. 2024

J Transl Med

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Backgrounds The incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10–20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy. Methods A total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored. Results Among the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs. Conclusions Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis.

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Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

Cited by 4 publications

References 37 publications

Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data

Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data

Real-world results of CAR T-cell therapy for large B-cell lymphoma with CNS involvement: a GLA/DRST study

Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia

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