scholarly journals Efficacy and Safety of Axicabtagene Ciloleucel and Tisagenlecleucel Administration in Lymphoma Patients With Secondary CNS Involvement: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
XiaoQin Wu ◽  
XinYue Zhang ◽  
RenDe Xun ◽  
MengSi Liu ◽  
Zhen Sun ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Risk Of Bias ◽  
Cns Lymphoma ◽  
Efficacy And Safety ◽  
Cns Involvement ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

BackgroundThe efficacy and safety of chimeric antigen receptor T (CAR-T) cell therapy in the treatment of non-Hodgkin’s lymphoma has already been demonstrated. However, patients with a history of/active secondary central nervous system (CNS) lymphoma were excluded from the licensing trials conducted on two widely used CAR-T cell products, Axicabtagene ciloleucel (Axi-cel) and Tisagenlecleucel (Tisa-cel). Hence, the objective of the present review was to assess whether secondary CNS lymphoma patients would derive a benefit from Axi-cel or Tisa-cel therapy, while maintaining controllable safety.MethodTwo reviewers searched PubMed, Embase, Web of Science, and Cochrane library independently in order to identify all records associated with Axi-cel and Tisa-cel published prior to February 15, 2021. Studies that included secondary CNS lymphoma patients treated with Axi-cel and Tisa-cel and reported or could be inferred efficacy and safety endpoints of secondary CNS lymphoma patients were included. A tool designed specifically to evaluate the risk of bias in case series and reports and the ROBINS-I tool applied for cohort studies were used.ResultsTen studies involving forty-four patients were included. Of these, seven were case reports or series. The other three reports were cohort studies involving twenty-five patients. Current evidence indicates that secondary CNS lymphoma patients could achieve long-term remission following Axi-cel and Tisa-cel treatment. Compared with the non-CNS cohort, however, progression-free survival and overall survival tended to be shorter. This was possibly due to the relatively small size of the CNS cohort. The incidence and grades of adverse effects in secondary CNS lymphoma patients resembled those in the non-CNS cohort. No incidences of CAR-T cell-related deaths were reported. Nevertheless, the small sample size introduced a high risk of bias and prevented the identification of specific patients who could benefit more from CAR-T cell therapy.ConclusionSecondary CNS lymphoma patients could seem to benefit from both Axi-cel and Tisa-cel treatment, with controllable risks. Thus, CAR-T cell therapy has potential as a candidate treatment for lymphoma patients with CNS involvement. Further prospective studies with larger samples and longer follow-up periods are warranted and recommended.

scholarly journals Decitabine in Combination with Fludarabine and Cyclophosphamide As Lymphodepletion Regimen Followed By CD19/CD22 Bispecific Targeted CAR-T Therapy Significantly Improves Survival in Relapsed/Refractory B-ALL Patients: A Pilot Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1754-1754
Author(s):  
Yunju Ma ◽  
Changju Qu ◽  
Haiping Dai ◽  
Sining Liu ◽  
Qingya Cui ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Efficacy And Safety ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background: CD19/CD22 bispecific targeted chimeric antigen receptor T cell (CAR-T) therapy has achieved impressive progress in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL), with high rates of complete remission (CR). However, T cell exhaustion caused by de novo DNA methylation restricts the capacity of CAR-T. Decitabine (DAC), a DNA methyltransferase inhibitor, has been demonstrated to reverse exhaustion-associated DNA-methylation programs, promote the rejuvenation of CAR-T cells and enhance anti-leukemic effect of CAR-T cells in vitro. To date, there are limited reports about the use of DAC as a part of lymphodepletion therapy before CAR-T cell therapy. Here, we report efficacy and safety of DAC in combination with fludarabine and cyclophosphamide (FC) regimen followed by CD19/CD22 CAR-T cell therapy for patients with R/R B-ALL. Method:We conducted a phase 1/2 clinical trial to investigate the efficacy and safety of CD19/CD22 CAR-T in the treatment of R/R B-ALL (NCT03614858). Fourteen patients were treated with DAC (total dose 100mg/m 2 in 3 days) followed by FC regimen (fludarabine 30mg/m 2 × 3d and cyclophosphamide 300mg/m 2 × 3d) (DAC group), while twelve patients received FC regimen prior to CAR-T cell infusion (CON group). A total of 1 or 2 × 10 7 CAR-T cells/kg were infused at dose escalation. Results: Baseline characteristics of patients in both groups had no significant differences except previous hematopoietic stem cell transplantation (HSCT). There were more patients with relapse after HSCT in DAC group (42.9% versus 0%, P=0.017). All patients did not achieve remission before lymphodepletion. The day 28 CR rates were 100% in DAC group and 91.7% in CON group. Furthermore, minimal residual disease (MRD) negative CR rates were 71.4% and 58.3%, respectively (P = 0.683). There was no significant difference in the proportion of nontransplant patients after CAR-T treatment between two groups. Among the nontransplant patients after CAR-T infusion in DAC group, 16.7% (1/6) of patients relapsed at 4 months. However, among 4 nontransplant patients in CON group, 1 patient achieved NR after CAR-T therapy and 3 patients relapsed at 1.5, 5, and 10 months. There were significant differences in overall survival (OS) and leukemia-free survival (LFS) between two groups: 3-year OS, 88.9% (DAC) versus 33.3% (CON), P = 0.01 and 3-year LFS, 92.3% (DAC) versus 21.8% (CON), P = 0.002. Multivariable analysis showed that addition of DAC to the lymphodepletion regimen was associated with better OS (hazard ratio [HR] 0.107, [95% CI, 0.013-0.875], P = 0.037) and LFS (HR 0.081, [95% CI, 0.01-0.65], P = 0.018). Cytokine release syndrome was observed in all patients. Conclusion: In summary, DAC in combination with FC regimen followed by CD19CD22 CAR-T cells was feasible and well tolerated. Our study demonstrated DAC combined with FC was an independent prognostic factor correlated with better survival in relapsed/refractory B-ALL patients. Disclosures No relevant conflicts of interest to declare.

CD19-Directed CAR T Cells Treatment in a Patient With Refractory DLBCL and CNS Involvement

2019 ◽  
pp. 16-21
Author(s):  
Alexander Ring ◽  
Antonia Maria Müller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

ABSTRACT Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common neoplasm of the lymphatic system. Treatment and clinical management are difficult in the relapsed/refractory (R/R) setting. Chimeric antigen receptor (CAR) T cells are genetically engineered using autologous patient lymphocytes and have shown very promising results in the treatment of relapsed and refractory cases of DLBCL. Methods: A 64-year-old male patient with refractory DLBCL and central nervous system (CNS) involvement after 9 lines of therapy was treated with CD19-specific CAR T cell therapy at the Department of medical oncology and hematology at the University Hospital of Zurich and followed-up for 10 weeks. Results: Autologous lymphocytes were successfully harvested and transfected/expanded for CAR T cell production. Conditioning chemotherapy and CAR T infusion was well tolerated. Post-infusion side effects were mild (cytokine release syndrome [CRS] grade 1−2), with limited signs of neurotoxicity. Ten weeks after CAR T cell therapy, an excellent response could be documented via PET-CT. The CNS lesion disappeared as assessed via cranial MRI. Conclusion: CD19-targeted CAR T cell therapy is a revolutionary treatment option for heavily pre-treated R/R DLBCL even in the setting of CNS involvement.

The efficacy and safety of CAR-T cell therapy in patients with refractory ALL and concomitant HBV infection

Leukemia ◽  
2020 ◽  
Vol 34 (10) ◽  
pp. 2790-2793
Author(s):  
Peilong Lai ◽  
Xiaomei Chen ◽  
Le Qin ◽  
Zhiwu Jiang ◽  
Chenwei Luo ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Hbv Infection ◽  
Efficacy And Safety ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

CAR T-cell therapy: Balance of efficacy and safety

2017 ◽  
Vol 51 (2) ◽  
pp. 237-250 ◽  
Author(s):  
S. V. Kulemzin ◽  
V. V. Kuznetsova ◽  
M. Mamonkin ◽  
A. V. Taranin ◽  
A. A. Gorchakov
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Efficacy And Safety ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt Lymphoma

2021 ◽  
Author(s):  
Ying Liu ◽  
Biping Deng ◽  
Bo Hu ◽  
Wenqun Zhang ◽  
Qing Zhu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Burkitt Lymphoma ◽  
Cns Involvement ◽  
Durable Response ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Single antigen-targeted chimeric antigen receptor (CAR) T-cell therapy may be insufficient to induce a durable response in pediatric aggressive B-cell lymphomas. The clinical trial (ChiCTR1800014457) examined the feasibility of sequential different B cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Twenty-three patients received the first CD19 CAR T-cell infusion. The patients who did not achieve an ongoing complete response sequentially underwent one or more additional infusions of CAR T-cell targeting CD22 followed by CD20 according to their disease status and CAR T-cell persistence after each infusion. The median time from the last infusion to cutoff date was 17 months (range, 15 to 23). The estimated 18-month complete response rate was 78% (95% confidence interval [CI], 54 to 91). The estimated 18-month progression-free survival rate was 78% (95% CI, 55 to 90), with 78% (95% CI, 37 to 94) in patients with bulky diseases and 60% (95% CI, 25 to 83) in patients with central nervous system (CNS) involvement. During the first CD19 CAR T-cell infusion, grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity occurred in 34.8% and 21.7% of all patients, respectively. During subsequent infusions, few incidences of higher than grade 2 CRS and neurotoxicity were observed. All adverse events were reversible. The severity of neurotoxicity was not significantly different between patients with CNS and non-CNS involvement. Sequential CAR T-cell therapy may result in a durable response and is safe in pediatric refractory/relapsed Burkitt lymphoma. Patients with CNS involvement may benefit from sequential CAR T-cell therapy. This trial was registered at www.chictr.org.cn/index.aspx as ChiCTR1800014457.

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