Outcomes After Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults With B-Cell Acute Lymphoblastic Leukemia

Media type: E-Article
Title: Outcomes After Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults With B-Cell Acute Lymphoblastic Leukemia
Contributor: Schultz, Liora M.; Eaton, Anne; Baggott, Christina; Rossoff, Jenna; Prabhu, Snehit; Keating, Amy K.; Krupski, Christa; Pacenta, Holly; Philips, Christine L.; Talano, Julie-An; Moskop, Amy; Baumeister, Susanne H.C.; Myers, Gary Douglas; Karras, Nicole A.; Brown, Patrick A.; Qayed, Muna; Hermiston, Michelle; Satwani, Prakash; Wilcox, Rachel; Rabik, Cara A.; Fabrizio, Vanessa A.; Chinnabhandar, Vasant; Kunicki, Michael; Mavroukakis, Sharon; [...]
imprint: American Society of Clinical Oncology (ASCO), 2023
Published in: Journal of Clinical Oncology
Language: English
DOI: 10.1200/jco.22.01076
ISSN: 0732-183X; 1527-7755
Keywords: Cancer Research ; Oncology
Origination:
Footnote:
Description: <jats:sec><jats:title>PURPOSE</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> 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. </jats:p></jats:sec>
Access State: Open Access

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