T cells expressing anti-CD19 chimeric antigen receptors ( CARs ) can cause complete remissions of relapsed lymphoma.
The first clinical trial of anti-CD19 CAR T cells was conducted to show responses against lymphoma.
This CAR was later developed as Axicabtagene ciloleucel ( Axi-cel;Yescarta ).
It has been assessed the long-term durability of remissions and the long-term adverse effects after anti-CD19 CAR T-cell therapy.
Between 2009 and 2015, researchers have treated 43 patients with anti-CD19 CAR T cells preceded by conditioning chemotherapy of Cyclophosphamide plus Fludarabine.
Three patients were re-treated for a total of 46 CAR T-cell treatments.
Twenty-eight patients had aggressive lymphoma ( diffuse large B-cell lymphoma or primary mediastinal B cell lymphoma ), eight patients had low-grade lymphoma ( five with follicular lymphoma and 1 each with splenic marginal zone lymphoma, mantle cell lymphoma, and unspecified low-grade non-Hodgkin lymphoma ), and seven patients had chronic lymphocytic leukemia ( CLL ).
Patients were treated in three cohorts that differed in the CAR T-cell production process and conditioning chemotherapy dose.
Of the 43 treated patients, 63% had chemotherapy-refractory lymphoma. Patients had received a median of 4 previous lines of therapy.
The median CAR+ T cell dose per kilogram was 2X10^6.
The overall remission rate was 76% with 54% complete remissions ( CR ) and 22% partial remissions ( PR ).
Patients with CR had higher median peak blood CAR levels ( 86 CAR+ cells/µL ) than those who did not have CR ( 16 CAR+ cells/µL, P= 0.0041 ).
Long-term adverse effects were rare except for B-cell depletion and hypogammaglobulinemia, which both improved over time.
In conclusion, this is the longest follow-up study of patients who have received anti-CD19 CAR T cells.
Anti-CD19 CAR T cells cause highly durable remissions of relapsed B-cell lymphoma and chronic lymphocytic leukemia, and long-term adverse effects of anti-CD19 CAR T cells were rare and usually mild. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020