Faculty Collaboration Database

Outcomes After Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults With B-Cell Acute Lymphoblastic Leukemia. J Clin Oncol 2023 Jan 10;41(2):354-363

Date

09/16/2022

Pubmed ID

36108252

Pubmed Central ID

PMC9839307

DOI

10.1200/JCO.22.01076

Scopus ID

2-s2.0-85145668660 (requires institutional sign-in at Scopus site)   25 Citations

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.

Author List

Schultz LM, Eaton A, Baggott C, Rossoff J, Prabhu S, Keating AK, Krupski C, Pacenta H, Philips CL, Talano JA, Moskop A, Baumeister SHC, Myers GD, Karras NA, Brown PA, Qayed M, Hermiston M, Satwani P, Wilcox R, Rabik CA, Fabrizio VA, Chinnabhandar V, Kunicki M, Mavroukakis S, Egeler E, Li Y, Mackall CL, Curran KJ, Verneris MR, Laetsch TW, Stefanski H

Authors

Amy Moskop MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Antigens, CD19
Child
Chronic Disease
Humans
Immunotherapy, Adoptive
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Receptors, Antigen, T-Cell
Recurrence
Retrospective Studies
Young Adult