Contributions
Abstract: EP533
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
The Chimeric antigen receptor (CAR) T-cell therapy has shown very promising future in relapsed/refractory B-cell lymphoma while the central nervous system lymphoma(CNSL) remained one of exclusion criterion in CAR T-cell therapy due to its fatal neurotoxicity.Recently several studies reported CAR T-cell therapy was safe and effective in treatment of advanced CNS disease, however, its resultant remission seemed short-lasting.
Aims
1.Investigate the effect and safety of CAR T-cell therapy in advanced refractory/relapsed central nervous system B-cell lymphoma(R/RCNSBL).2.Compare effects of combination of autolougs hematopoietic stem cell transplantation(ASCT)with CAR T-cell therapy, and sequential multiple targets of CAR T-cell therapy towards survival of the subjects.
Methods
17 patients (aged 19-66 years) with advanced R/RCNSBL were enrolled from 01/10/2018 to 01/10/2020,and are reviewed. Prior to administration of CAR T-cell therapy, all of the patients received chemotherapy and targeted drugs treatment to reduce tumor loads. Only patients who had responded to chemotherapy would be treated with stem cell mobilization and collection. The ASCT combined with CD19, CD20 or CD22 CAR T-cell therapy would be then administered to patients whose stem cells were successfully collected or had been already prepared. While other patients would be given with sequential therapy with targeting CD19, CD20 or CD19-22 CAR T-cell therapy. After CAR T-cells were infused, mannitol was also given for prophylaxis. The T-cells with specific CAR expression in peripheral blood and cerebrospinal fluid were dynamically detected by flow cytometry. After CAR T-cells infusion, PET-CT, PET-MRI or contrast-enhanced MRI were performed every 3 months. Patients were followed up till 1/31/2021
Results
1.8 cases of 17 patients, who completed treatment of ASCT and CAR T-cell therapy, and the other 9 cases with completed multi-target sequential therapy. 2.The incidence of cytokine release syndrome (CRS) was 94.11%, of which 41.17% was severe CRS(≥grade 3), as the incidence of immune effector cells associated neurologic toxicity(ICANS )was 35.29%, of which 29.41% was severe ICANS. In comparison, in ASCT group and non-ASCT group, the incidence of severe CRS(≥grade 3）were 50% and 33.33%(P=0.486),respectively;and that of severe ICANS (≥grade 3) were 25% and 33.33% (p=0.14), respectively. There were no death related to the treatment.3. In 3 months, complete remission rate was 64.70% (11/17), partial remission rate was 5.88% (1/17 ) and the objective response rate was 70.59% (12/17). The remission rate of the ASCT group was higher than that of the non-ASCT group (100% vs 44.4%, P < 0.01). the median of progression-free survival length(PFS) was 8 months (ranging 2-17 months). The overall survival length (OS) was 6 to 21 months. In comparison, in the group of ASCT combined with CAR T-cells therapy, patients in remission had longer PFS (11 months vs 4 months, P=0.02), with no significant difference in the overall survival length between the two groups ( 11 months vs 9 months, P =0.52).
Conclusion
1.The CAR T-cell therapy could augment its efficacy in treatment of advanced R/RCNSBL.2.The neurotoxicity of CAR T- cells therapy could be mitigated, and there was no death related to treatment.3.The combined treatment of ASCT and CAR T-cell therapy could increase sustained response and longer survival length.
Keyword(s): Autologous hematopoietic stem cell transplantation, Cellular immunity, CNS lymphoma
Abstract: EP533
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
The Chimeric antigen receptor (CAR) T-cell therapy has shown very promising future in relapsed/refractory B-cell lymphoma while the central nervous system lymphoma(CNSL) remained one of exclusion criterion in CAR T-cell therapy due to its fatal neurotoxicity.Recently several studies reported CAR T-cell therapy was safe and effective in treatment of advanced CNS disease, however, its resultant remission seemed short-lasting.
Aims
1.Investigate the effect and safety of CAR T-cell therapy in advanced refractory/relapsed central nervous system B-cell lymphoma(R/RCNSBL).2.Compare effects of combination of autolougs hematopoietic stem cell transplantation(ASCT)with CAR T-cell therapy, and sequential multiple targets of CAR T-cell therapy towards survival of the subjects.
Methods
17 patients (aged 19-66 years) with advanced R/RCNSBL were enrolled from 01/10/2018 to 01/10/2020,and are reviewed. Prior to administration of CAR T-cell therapy, all of the patients received chemotherapy and targeted drugs treatment to reduce tumor loads. Only patients who had responded to chemotherapy would be treated with stem cell mobilization and collection. The ASCT combined with CD19, CD20 or CD22 CAR T-cell therapy would be then administered to patients whose stem cells were successfully collected or had been already prepared. While other patients would be given with sequential therapy with targeting CD19, CD20 or CD19-22 CAR T-cell therapy. After CAR T-cells were infused, mannitol was also given for prophylaxis. The T-cells with specific CAR expression in peripheral blood and cerebrospinal fluid were dynamically detected by flow cytometry. After CAR T-cells infusion, PET-CT, PET-MRI or contrast-enhanced MRI were performed every 3 months. Patients were followed up till 1/31/2021
Results
1.8 cases of 17 patients, who completed treatment of ASCT and CAR T-cell therapy, and the other 9 cases with completed multi-target sequential therapy. 2.The incidence of cytokine release syndrome (CRS) was 94.11%, of which 41.17% was severe CRS(≥grade 3), as the incidence of immune effector cells associated neurologic toxicity(ICANS )was 35.29%, of which 29.41% was severe ICANS. In comparison, in ASCT group and non-ASCT group, the incidence of severe CRS(≥grade 3）were 50% and 33.33%(P=0.486),respectively;and that of severe ICANS (≥grade 3) were 25% and 33.33% (p=0.14), respectively. There were no death related to the treatment.3. In 3 months, complete remission rate was 64.70% (11/17), partial remission rate was 5.88% (1/17 ) and the objective response rate was 70.59% (12/17). The remission rate of the ASCT group was higher than that of the non-ASCT group (100% vs 44.4%, P < 0.01). the median of progression-free survival length(PFS) was 8 months (ranging 2-17 months). The overall survival length (OS) was 6 to 21 months. In comparison, in the group of ASCT combined with CAR T-cells therapy, patients in remission had longer PFS (11 months vs 4 months, P=0.02), with no significant difference in the overall survival length between the two groups ( 11 months vs 9 months, P =0.52).
Conclusion
1.The CAR T-cell therapy could augment its efficacy in treatment of advanced R/RCNSBL.2.The neurotoxicity of CAR T- cells therapy could be mitigated, and there was no death related to treatment.3.The combined treatment of ASCT and CAR T-cell therapy could increase sustained response and longer survival length.
Keyword(s): Autologous hematopoietic stem cell transplantation, Cellular immunity, CNS lymphoma