Contributions
Abstract: PB1435
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
In the process of chimeric antigen receptor (CAR) T cells therapy, it is necessary to carry out pretreatment chemotherapy to reduce lymphocytes called lymphodepleting chemotherapy before infusion of CAR T cells, which makes CAR T cells continuously expanding in vivo, plays an anti-tumor effect as well. For the patients of relapsed and refractory B-cell lymphoma (R&R BCL) treated with CAR T, the preferred lymphodepleting chemotherapy should have the dual effect of clearing lymphocytes and reducing tumor load. Bendamustine was reported to treat some R&R BCL, as well acting on lymphocyte clearing.
Aims
To investicate the clinical application of bendamustine as the pretreatment prior to CAR T cells infusion, and to examine its safety and therapeutic effect.
Methods
Twenty-one patients in our cohort were enrolled in this study. All of them were refractory and relapsed patients with poor response to several second-line chemotherapy. The mean age of these 21 patients was 50 years old. Twelve patients were male and 9 patients were female. Nineteen patients were defuse large B cell lymphoma (12 patients were non-GCB and 7 patients were GCB), One patient was follicular lymphoma, and one was Burkitt Lymphoma. About 85.7% patients (18/21) were in stage III-IV, 71.4% patients (15/21) were ECOG≥2. Bendamustine (90 mg/m2) were used to deplete lymphocytes on days -4~-3 before infusion of CAR T cells (day 0). The CAR T cells for treatment were CD19 or CD20 or CD22 specific chimeric antigen receptor T cells. Average dose of CAR T cells infusion was 2.25×106/kg. CAR T cells in the PB were measured on day 0, 7, 11, 15 and 30, or as necessary by Flow cytometry.
Results
In the bendamustine group, the average peak number of CAR T cells expansion in vivo was 1.97×108/L. There were few serious adverse reactions except nausea and vomiting during chemotherapy. The occurrence rate of CRS above grade 2 was 33.3% （7/21） and ICANS above grade 3 was 9.5% （2/21）. Three months after CAR T cells infusion, 38.1% patients (8/21) achieved CR, 47.6% patients (10/21) with PR. So the ORR was 85.7%.
Among the 21 patients, 5 patients were treated with CAR T cells twice within 6 months. Fudalabine combined with cyclophosphamide (FC) was chosen for the first lymphodepleting regimen and bendamustine for the second. Bendamustine reduced the number of lymphocytes by 82.3%, while it was 88.6% for FC (P >0.05). Overall the bendamustine regimen was inferior to FC in term of the CAR T cell proliferation rate. There was no significantly difference between these two groups about the occurrence rate of CRS. Regarding CR rate, bendamustine is considered to be superior to FC group.
Conclusion
Bendamustine can be used as a favorable lymphodepleting chemotherapy drug prior to CAR T.
Key words：Bendamustine， Fludarabine， CAR T， lymphodepleting chemotherapy.
Keyword(s):
Abstract: PB1435
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
In the process of chimeric antigen receptor (CAR) T cells therapy, it is necessary to carry out pretreatment chemotherapy to reduce lymphocytes called lymphodepleting chemotherapy before infusion of CAR T cells, which makes CAR T cells continuously expanding in vivo, plays an anti-tumor effect as well. For the patients of relapsed and refractory B-cell lymphoma (R&R BCL) treated with CAR T, the preferred lymphodepleting chemotherapy should have the dual effect of clearing lymphocytes and reducing tumor load. Bendamustine was reported to treat some R&R BCL, as well acting on lymphocyte clearing.
Aims
To investicate the clinical application of bendamustine as the pretreatment prior to CAR T cells infusion, and to examine its safety and therapeutic effect.
Methods
Twenty-one patients in our cohort were enrolled in this study. All of them were refractory and relapsed patients with poor response to several second-line chemotherapy. The mean age of these 21 patients was 50 years old. Twelve patients were male and 9 patients were female. Nineteen patients were defuse large B cell lymphoma (12 patients were non-GCB and 7 patients were GCB), One patient was follicular lymphoma, and one was Burkitt Lymphoma. About 85.7% patients (18/21) were in stage III-IV, 71.4% patients (15/21) were ECOG≥2. Bendamustine (90 mg/m2) were used to deplete lymphocytes on days -4~-3 before infusion of CAR T cells (day 0). The CAR T cells for treatment were CD19 or CD20 or CD22 specific chimeric antigen receptor T cells. Average dose of CAR T cells infusion was 2.25×106/kg. CAR T cells in the PB were measured on day 0, 7, 11, 15 and 30, or as necessary by Flow cytometry.
Results
In the bendamustine group, the average peak number of CAR T cells expansion in vivo was 1.97×108/L. There were few serious adverse reactions except nausea and vomiting during chemotherapy. The occurrence rate of CRS above grade 2 was 33.3% （7/21） and ICANS above grade 3 was 9.5% （2/21）. Three months after CAR T cells infusion, 38.1% patients (8/21) achieved CR, 47.6% patients (10/21) with PR. So the ORR was 85.7%.
Among the 21 patients, 5 patients were treated with CAR T cells twice within 6 months. Fudalabine combined with cyclophosphamide (FC) was chosen for the first lymphodepleting regimen and bendamustine for the second. Bendamustine reduced the number of lymphocytes by 82.3%, while it was 88.6% for FC (P >0.05). Overall the bendamustine regimen was inferior to FC in term of the CAR T cell proliferation rate. There was no significantly difference between these two groups about the occurrence rate of CRS. Regarding CR rate, bendamustine is considered to be superior to FC group.
Conclusion
Bendamustine can be used as a favorable lymphodepleting chemotherapy drug prior to CAR T.
Key words：Bendamustine， Fludarabine， CAR T， lymphodepleting chemotherapy.
Keyword(s):