CAR-T

Factors Associated with Outcomes After a Second CD19-Targeted CAR T-Cell Infusion for Refractory B-Cell Malignancies

Factors Associated with Outcomes After a Second CD19-Targeted CAR T-Cell Infusion for Refractory B-Cell Malignancies

January 21, 2021

CD19 CAR-T therapy have shown significant activity for relapsed / refractory (R/R) B-cell malignancies. Second infusions of CD19 CAR T cells (CART2) have been postulated as an approach to improve outcomes given lack of durable responses. In the referenced study, data from 44 patients with R/R B-cell malignancies (ALL, n = 14; CLL, n = 9; nHL, n = 21) who were treated with CART2 in a phase 1/2 trial at Fred Hutchinson Cancer Research Center, Seattle, WA are reviewed. Despite a CART2 dose increase in 82% of patients, a low incidence of severe toxicity after CART2 (grade ≥3 cytokine release syndrome, 9%; grade ≥3 neurotoxicity, 11%) were observed.

The investigators reported that after CART2, CRs were achieved in 22% of CLL, 19% of nHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. The addition of fludarabine to cyclophosphamide-based lymphodepletion before CART1 and an increase in the CART2 dose compared with CART1 were independently associated with higher ORRs and longer progression-free survival after CART2.

Durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide plus fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose were observed. The investigators concluded that “identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR-T cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies.”

Reference:

https://ashpublications.org/blood/article-abstract/137/3/323/463850/Factors-associated-with-outcomes-after-a-second?redirectedFrom=fulltext

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