Lack of response to tisagenlecleucel is associated with poor overall survival (OS) among children and young adults with B-cell acute lymphoblastic leukemia (B-ALL), according to a retrospective study published in the Journal of Clinical Oncology.

The study also showed that patients with relapse after tisagenlecleucel can benefit from salvage therapy, but CD19-negative relapse is associated with poor OS.

The multicenter study included data from 80 children and young adults with B-ALL whose disease failed to respond or recurred after tisagenlecleucel treatment. The median age among nonresponders and patients who relapsed was 10 years and 12 years, respectively. In both cohorts, the median number of relapses prior to tisagenlecleucel was 2.


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OS outcomes were poor among nonresponders, with a 12-month OS rate of 19% and a median OS of 160 days. Nearly all nonresponding patients demonstrated a high burden of disease prior to their chimeric antigen recepter (CAR) T-cell infusion that persisted after the infusion.

In the relapsed cohort, the median time to relapse was 101 days (range, 30-645), and 84% of patients had bone marrow involvement. Loss of B-cell aplasia preceded relapse by a median of 84 days in 15 of 25 evaluable patients. Of patients evaluable for CD19 expression, 41% demonstrated downregulation or loss of expression at relapse.

Negative CD19 expression was an independent predictor of relapse in a multivariate analysis (hazard ratio [HR], 2.83; 95% CI, 1.11-7.20; P =.03). Relapse within 6 months after tisagenlecleucel treatment was associated with shorter OS (HR, 4.75; 95% CI, 1.86-12.1; P =.001).

Salvage therapy was administered to 88% of patients who relapsed. Salvage most commonly consisted of chemotherapy or inotuzumab, followed by CAR T-cell reinfusion, blinatumomab, and other therapies. A complete response was achieved by 56% of patients after their first salvage therapy, including 64% treated with inotuzumab and 78% treated with CD19-CAR reinfusion.

“This supports the need for relapse mitigation strategies, yet demonstrates the possibility of salvage in the relapse post-tisagenlecleucel setting,” the study authors wrote.

Patients whose disease relapsed after tisagenlecleucel had a 12-month OS of 52%, which differed depending on CD19 expression. Positive expression was associated with a higher rate of 12-month OS, at 68%, compared with 30% among patients negative for CD19 expression.

“We identify patients with CD19- relapse post-tisagenlecleucel to be a high-risk patient population and highlight the need for the systematic study of salvage regimens in the post-tisagenlecleucel nonresponse and relapse settings,” the authors wrote.

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

Reference

Schultz LM, Eaton A, Baggott C, et al. Outcomes after nonresponse and relapse post-tisagenlecleucel in children, adolescents, and young adults with B-cell acute lymphoblastic leukemia. J Clin Oncol. Published online September 15, 2022. doi: 10.1200/JCO.22.01076

This article originally appeared on Hematology Advisor