Contributions
Abstract: EP346
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Although CD19-specific chimeric antigen receptor (CAR) T-cell therapy has achieved high complete remission rates in relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL), some patients relapse after CAR-T. For CD19-positive relapsed B-ALL, reinfusion of CD19-CART cells is a salvage treatment option. At present, most of CD19 CART cell products are murinized (mCD19-CART), reinfusion of mCD19-CART may not be effective owing to anti-mouse scFv antibody caused by mCD19-CAR. In this study, we used humanized CD19-CART (hCD19-CART) cells to treat relapsed B-ALL patients who had previously accepted mCD19-CART cells.
Aims
To evaluate the treatment efficacy of hCD19-CART cells for B-ALL patients relapsing after mCD19-CART therapy.
Methods
From January 2019 to October 2020, a total of 18 heavily treated adult and pediatric r/r B-ALL patients were enrolled. Seventeen patients were hematological relapse or with extramedullary diseases (EMD, n=6), 1 was minimal residual disease (MRD) relapse. All patients had accepted prior murinized-CD19 CAR-T therapy (once, n=15; twice, n=3), and relapsed with CD19 antigen expression identified by flow cytometer (FCM), 11 cases had a history of CD22 CAR-T therapy. CAR-T cells were produced by lentiviral vectors encoding second generation CARs composed of CD3ζ and 4-1BB. All patients accepted fludarabine and/or cyclophosphamide before cell infusion. The treatment effect was evaluated on day 30 after cell infusion, MRD was quantified by FCM and PCR for fusion gene, EMDs were evaluated by PET-CT/CT/ultrasound. The last follow-up was as of December 31, 2020. The informed consents were obtained in accordance with the Declaration of Helsinki.
Results
The median age of 18 patients was 19 (range, 4-49) years, including 10 adults and 8 children younger than 18 years old, 2 with BCR-ABL fusion gene and 2 with TP53 gene mutation, 10 underwent allogeneic transplantation. The median dose of infused CAR-T cells was 5.0 x 105/kg (range, 1.0-18.0 x 105/kg). Cytokine release syndrome (CRS) occurred in all patients, including 14 with grade 1, 3 with grade 2 and 1 with grade 4 CRS. Except for supportive care, 9 patients were administered steroids, 3 were given additional plasmapheresis. There were no neurotoxicity and treatment-related death.
On day 30 after T-cell infusion, 12 (67%) cases achieved complete remission (CR, 11 MRD-negative CR) and 6 had no response (NR). In 12 CR patients, 10 followed by allogeneic hematopoietic cell transplantation (allo-HCT, 3 were second HCT) in 1.3-2.3 months after CAR-T, 9 (9/10, 90%) patients remained in CR with a median remission period of 6.7 months (2.4-22 months), only 1 relapsed at 3 months after HCT. Another 2 CR patients did not undergo HCT, 1 relapsed at 9.9 months and 1 remained in CR for 8.9 months. Among 6 NR patients, 3 died of disease progression, and 3 accepted salvage transplantation (all were second HCT), of them, 2 relapsed at 4 and 8.5 months after HCT, and 1 had survived for 9.2 months.
Conclusion
The salvage treatment of humanized CD19-CART cells resulted in a 67% CR in CD19-positive relapsed B-ALL patients who had a prior murinized CD19-CART therapy, and transplantation followed-by hCD19-CART allowed 90% CR patients to obtain a remission of 2.4-22 months. The prognosis of NR patients was still poor.
Keyword(s): Acute lymphoblastic leukemia, Cellular therapy
Abstract: EP346
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Although CD19-specific chimeric antigen receptor (CAR) T-cell therapy has achieved high complete remission rates in relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL), some patients relapse after CAR-T. For CD19-positive relapsed B-ALL, reinfusion of CD19-CART cells is a salvage treatment option. At present, most of CD19 CART cell products are murinized (mCD19-CART), reinfusion of mCD19-CART may not be effective owing to anti-mouse scFv antibody caused by mCD19-CAR. In this study, we used humanized CD19-CART (hCD19-CART) cells to treat relapsed B-ALL patients who had previously accepted mCD19-CART cells.
Aims
To evaluate the treatment efficacy of hCD19-CART cells for B-ALL patients relapsing after mCD19-CART therapy.
Methods
From January 2019 to October 2020, a total of 18 heavily treated adult and pediatric r/r B-ALL patients were enrolled. Seventeen patients were hematological relapse or with extramedullary diseases (EMD, n=6), 1 was minimal residual disease (MRD) relapse. All patients had accepted prior murinized-CD19 CAR-T therapy (once, n=15; twice, n=3), and relapsed with CD19 antigen expression identified by flow cytometer (FCM), 11 cases had a history of CD22 CAR-T therapy. CAR-T cells were produced by lentiviral vectors encoding second generation CARs composed of CD3ζ and 4-1BB. All patients accepted fludarabine and/or cyclophosphamide before cell infusion. The treatment effect was evaluated on day 30 after cell infusion, MRD was quantified by FCM and PCR for fusion gene, EMDs were evaluated by PET-CT/CT/ultrasound. The last follow-up was as of December 31, 2020. The informed consents were obtained in accordance with the Declaration of Helsinki.
Results
The median age of 18 patients was 19 (range, 4-49) years, including 10 adults and 8 children younger than 18 years old, 2 with BCR-ABL fusion gene and 2 with TP53 gene mutation, 10 underwent allogeneic transplantation. The median dose of infused CAR-T cells was 5.0 x 105/kg (range, 1.0-18.0 x 105/kg). Cytokine release syndrome (CRS) occurred in all patients, including 14 with grade 1, 3 with grade 2 and 1 with grade 4 CRS. Except for supportive care, 9 patients were administered steroids, 3 were given additional plasmapheresis. There were no neurotoxicity and treatment-related death.
On day 30 after T-cell infusion, 12 (67%) cases achieved complete remission (CR, 11 MRD-negative CR) and 6 had no response (NR). In 12 CR patients, 10 followed by allogeneic hematopoietic cell transplantation (allo-HCT, 3 were second HCT) in 1.3-2.3 months after CAR-T, 9 (9/10, 90%) patients remained in CR with a median remission period of 6.7 months (2.4-22 months), only 1 relapsed at 3 months after HCT. Another 2 CR patients did not undergo HCT, 1 relapsed at 9.9 months and 1 remained in CR for 8.9 months. Among 6 NR patients, 3 died of disease progression, and 3 accepted salvage transplantation (all were second HCT), of them, 2 relapsed at 4 and 8.5 months after HCT, and 1 had survived for 9.2 months.
Conclusion
The salvage treatment of humanized CD19-CART cells resulted in a 67% CR in CD19-positive relapsed B-ALL patients who had a prior murinized CD19-CART therapy, and transplantation followed-by hCD19-CART allowed 90% CR patients to obtain a remission of 2.4-22 months. The prognosis of NR patients was still poor.
Keyword(s): Acute lymphoblastic leukemia, Cellular therapy