07.05.22

Phenotypic Escape in CD19 -Directed Therapies

Bueno C, Barrena S, Bataller A, et al. CD34+CD19-CD22+ B-Cell Progenitors Might Underlie Phenotypic Escape in Patients Treated with CD19-Directed Therapies. Blood. 2022; (doi: 10.1182/blood.2021014840).

Researchers report that pre-leukemic CD34+CD19-CD22+ B-cell progenitors may be implicated in phenotypic escape following delivery of CD19-directed immunotherapies, knowledge that might help identify B-ALL patients at risk of CD19-targeted therapy failure. . Investigators report that CD34+CD19-CD22+ cells are present in diagnostic and relapsed bone marrow samples of approximately 70% of B-ALL patients. The size of this cell population is three times greater before treatment in patients who eventually relapse following CD19 chimeric antigen receptor (CAR) T-cell therapy. According to the team, CD34+CD19-CD22+ cells harbor the genetic anomalies observed at diagnosis and trigger leukemogenesis in vivo. The findings suggest that CD34/CD19/CD22 immunophenotyping may be useful in identifying B-ALL patients for whom CD19-directed immunotherapies may not work. Additionally, the work lends credibility to ongoing research evaluating CD19/CD22 dual targeting as a pathway for reducing the incidence of relapse among CD19 immunotherapy recipients.

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