Correlation of CD19 Expression With Responses and Relapse After CAR-T Therapy

Chimeric antigen receptor (CAR) T-cell therapy is more effective in a certain group of patients with B-cell acute lymphoblastic leukemia (B-ALL), according to a study to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (June 1-5, 2018; Chicago, IL).

Vinodh Pillai, MD, PhD, The Children’s Hospital of Philadelphia, and colleagues assessed whether pre-treatment CD19 expression level or prior targeted therapy impacts response to CAR-T therapy.

The study evaluated patients with B-ALL treated with CAR-T therapy from 2012-2017 at The Children’s Hospital of Philadelphia. CD19 in blasts were classified into three categories—dim, normal, or bright—compared to normal B-cells by flow cytometry. CD19 expression and immunophenotype of blasts pre- and post-CAR therapy were correlated with responses to CAR-T therapy. 

Researchers identified a total of 150 patients treated with CAR-T therapy, of which 10 were non-response, 20 were CD19 positive relapses, and 33 were CD19 negative relapses. Fifteen of the patients had received prior CD19 targeted therapy. 

Researchers reported that the rate of responses and relapses in CD19 dim B-ALL were not significantly different from the CD19 normal/bright group. However, prior CD19-targeted therapy was associated with a significantly higher rate of non-response and CD19 negative relapse compared to 25% in patients who did not receive any prior CD19-targeted therapy. 

Additionally, immunophenotype of CD19 positive relapse were identical to that of pre-therapy disease in 85% of cases, consistent with loss of CAR T-cells as the etiology of those relapses. Blasts from CD19 negative relapse patients did not show any CD19-negative events by flow prior to CAR-T therapy in 75% of cases, suggesting that CD19-negative blasts may be de novo events. 

“CAR T-cell therapy is effective in B-ALL with dim CD19 expression. Prior targeted therapy is associated with increased non-response and relapse, likely due to CD19 escape,” authors concluded. “CD19PR after CAR T-cell therapy are due to early loss of CAR T-cells while CD19NR are likely due to expansion of de novo CD19-negative B lymphoblasts under treatment pressure.”—Janelle Bradley