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A relapsed B-acute Lymphoblastic Leukemia Patient with Low CD19 Density Achieved Remission with a Low Dose of Blinatumomab After Repeated CAR-T Cell Failure: a case report

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Patients were still at a high risk of relapse after achieving complete remission by CAR-T therapy. The mechanisms underlying CD19+ relapse still remain to be further clarified in B-acute lymphoblastic leukemia (B-ALL). We reported a patient with B-ALL who relapsed at nine months after allogeneic stem cell transplantation. After two times of autologous anti-CD19 CAR-T infusion treatment, he recured with CD19 MRD positive the third time. CD19 antigen density was assessed for recurrence after a second CAR- T infusion and was found to be decreasing. The patient obtained MRD-negative (sCR4) on day 7 of treatment with the initial dose of Blinatumomab and remained negative throughout the four courses of maintenance treatment. Our case demonstrates that patients with CD19 + relapsed MRD treated with CD19-targeted CAR-T are still effective with low-dose Blinatumomab. The secondary infusion of CAR-T with 4-1BB domain may reduce the density of CD19 target antigen on the surface of tumor cells, resulting in the short maintenance of PFS. Treatment with Blinatumomab may not depend on CD19 target antigen density. Blinatumomab as a Bispecific T engager may act as an adaptor to improve T cell and CAR-T responses for patients relapsed after CAR-T therapy, which explained one possible cause of relapse after secondary CAR-T infusion and provided reference for salvage treatment strategies after CAR-T relapse.
Title: A relapsed B-acute Lymphoblastic Leukemia Patient with Low CD19 Density Achieved Remission with a Low Dose of Blinatumomab After Repeated CAR-T Cell Failure: a case report
Description:
Patients were still at a high risk of relapse after achieving complete remission by CAR-T therapy.
The mechanisms underlying CD19+ relapse still remain to be further clarified in B-acute lymphoblastic leukemia (B-ALL).
We reported a patient with B-ALL who relapsed at nine months after allogeneic stem cell transplantation.
After two times of autologous anti-CD19 CAR-T infusion treatment, he recured with CD19 MRD positive the third time.
CD19 antigen density was assessed for recurrence after a second CAR- T infusion and was found to be decreasing.
The patient obtained MRD-negative (sCR4) on day 7 of treatment with the initial dose of Blinatumomab and remained negative throughout the four courses of maintenance treatment.
Our case demonstrates that patients with CD19 + relapsed MRD treated with CD19-targeted CAR-T are still effective with low-dose Blinatumomab.
The secondary infusion of CAR-T with 4-1BB domain may reduce the density of CD19 target antigen on the surface of tumor cells, resulting in the short maintenance of PFS.
Treatment with Blinatumomab may not depend on CD19 target antigen density.
Blinatumomab as a Bispecific T engager may act as an adaptor to improve T cell and CAR-T responses for patients relapsed after CAR-T therapy, which explained one possible cause of relapse after secondary CAR-T infusion and provided reference for salvage treatment strategies after CAR-T relapse.

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