Outcomes after nonresponse and relapse post-tisagenlecleucel in children, adolescents, and young adults with B-cell acute lymphoblastic leukemia Journal Article
| Authors: | Schultz, L. M.; Eaton, A.; Baggott, C.; Rossoff, J.; Prabhu, S.; Keating, A. K.; Krupski, C.; Pacenta, H.; Philips, C. L.; Talano, J. A.; Moskop, A.; Baumeister, S. H. C.; Myers, G. D.; Karras, N. A.; Brown, P. A.; Qayed, M.; Hermiston, M.; Satwani, P.; Wilcox, R.; Rabik, C. A.; Fabrizio, V. A.; Chinnabhandar, V.; Kunicki, M.; Mavroukakis, S.; Egeler, E.; Li, Y.; Mackall, C. L.; Curran, K. J.; Verneris, M. R.; Laetsch, T. W.; Stefanski, H. |
| Article Title: | Outcomes after nonresponse and relapse post-tisagenlecleucel in children, adolescents, and young adults with B-cell acute lymphoblastic leukemia |
| Abstract: | PURPOSENonresponse 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.METHODSWe 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.RESULTSThe 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.CONCLUSIONWe 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. © American Society of Clinical Oncology. |
| Keywords: | adolescent; child; retrospective studies; young adult; recurrence; retrospective study; acute lymphoblastic leukemia; chronic disease; receptors, antigen, t-cell; recurrent disease; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; lymphocyte antigen receptor; antigens, cd19; humans; human; tisagenlecleucel t; precursor b-cell lymphoblastic leukemia-lymphoma |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 41 |
| Issue: | 2 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2023-01-10 |
| Start Page: | 354 |
| End Page: | 363 |
| Language: | English |
| DOI: | 10.1200/jco.22.01076 |
| PUBMED: | 36108252 |
| PROVIDER: | scopus |
| PMCID: | PMC9839307 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Export Date: 1 February 2023 -- Source: Scopus |
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