TY - JOUR
T1 - Outcomes after Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults with B-Cell Acute Lymphoblastic Leukemia
AU - Schultz, Liora M.
AU - Eaton, Anne
AU - Baggott, Christina
AU - Rossoff, Jenna
AU - Prabhu, Snehit
AU - Keating, Amy K.
AU - Krupski, Christa
AU - Pacenta, Holly
AU - Philips, Christine L.
AU - Talano, Julie An
AU - Moskop, Amy
AU - Baumeister, Susanne H.C.
AU - Myers, Gary Douglas
AU - Karras, Nicole A.
AU - Brown, Patrick A.
AU - Qayed, Muna
AU - Hermiston, Michelle
AU - Satwani, Prakash
AU - Wilcox, Rachel
AU - Rabik, Cara A.
AU - Fabrizio, Vanessa A.
AU - Chinnabhandar, Vasant
AU - Kunicki, Michael
AU - Mavroukakis, Sharon
AU - Egeler, Emily
AU - Li, Yimei
AU - Mackall, Crystal L.
AU - Curran, Kevin J.
AU - Verneris, Michael R.
AU - Laetsch, Theodore W.
AU - Stefanski, Heather
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/1/10
Y1 - 2023/1/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.22.01076
DO - 10.1200/JCO.22.01076
M3 - Article
C2 - 36108252
AN - SCOPUS:85145668660
SN - 0732-183X
VL - 41
SP - 354
EP - 363
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -