Outcomes After Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults With B-Cell Acute Lymphoblastic Leukemia.
Document Type
Article
Publication Date
1-10-2023
Identifier
DOI: 10.1200/JCO.22.01076
Abstract
Purpose: Nonresponse and relapse after CD19-chimeric antigen receptor (CAR) T-cell therapy continue to challenge survival outcomes. Phase II landmark data from the ELIANA trial demonstrated nonresponse and relapse rates of 14.5% and 28%, respectively, whereas use in the real-world setting showed nonresponse and relapse rates of 15% and 37%. Outcome analyses describing fate after post-CAR nonresponse and relapse remain limited. Here, we aim to establish survival outcomes after nonresponse and both CD19+ and CD19- relapses and explore treatment variables associated with inferior survival.
Methods: We conducted a retrospective multi-institutional study of 80 children and young adults with B-cell acute lymphoblastic leukemia experiencing nonresponse (n = 23) or relapse (n = 57) after tisagenlecleucel. We analyze associations between baseline characteristics and these outcomes and establish survival rates and salvage approaches.
Results: The overall survival (OS) at 12 months was 19% across nonresponders (n = 23; 95% CI, 7 to 50). Ninety-five percent of patients with nonresponse had high preinfusion disease burden. Among 156 morphologic responders, the cumulative incidence of relapse was 37% (95% CI, 30 to 47) at 12 months (CD19+; 21% [15 to 29], CD19-; 16% [11 to 24], median follow-up; 380 days). Across 57 patients experiencing relapse, the OS was 52% (95% CI, 38 to 71) at 12 months after time of relapse. Notably, CD19- relapse was associated with significantly decreased OS as compared with patients who relapsed with conserved CD19 expression (CD19- 12-month OS; 30% [14 to 66], CD19+ 12-month OS; 68% [49 to 92], P = .0068). Inotuzumab, CAR reinfusion, and chemotherapy were used as postrelapse salvage therapy with greatest frequency, yet high variability in treatment sequencing and responses limits efficacy analysis across salvage approaches.
Conclusion: We describe poor survival across patients experiencing nonresponse to tisagenlecleucel. In the post-tisagenlecleucel relapse setting, patients can be salvaged; however, CD19- relapse is distinctly associated with decreased survival outcomes.
Journal Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume
41
Issue
2
First Page
354
Last Page
363
MeSH Keywords
Humans; Child; Young Adult; Adolescent; Retrospective Studies; Receptors, Antigen, T-Cell; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Immunotherapy, Adoptive; Recurrence; Antigens, CD19; Chronic Disease
Keywords
Retrospective Studies; T-Cell Antigen Receptors; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Adoptive Immunotherapy; Recurrence; Antigens, CD19; Chronic Disease
Recommended Citation
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. 2023;41(2):354-363. doi:10.1200/JCO.22.01076
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