Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study Journal Article
| Authors: | Shah, B. D.; Ghobadi, A.; Oluwole, O. O.; Logan, A. C.; Boissel, N.; Cassaday, R. D.; Leguay, T.; Bishop, M. R.; Topp, M. S.; Tzachanis, D.; O’Dwyer, K. M.; Arellano, M. L.; Lin, Y.; Baer, M. R.; Schiller, G. J.; Park, J. H.; Subklewe, M.; Abedi, M.; Minnema, M. C.; Wierda, W. G.; DeAngelo, D. J.; Stiff, P.; Jeyakumar, D.; Dong, J.; Adhikary, S.; Zhou, L.; Schuberth, P. C.; Faghmous, I.; Masouleh, B. K.; Houot, R. |
| Article Title: | Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study |
| Abstract: | Background: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care. Methods: Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 106 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3. Results: After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients (N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with > 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients (N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 (N = 49) and matched historical controls (N = 40) was 25.4 and 5.5 months, respectively. Conclusions: These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population. Trial Registration: NCT02614066. © 2022, The Author(s). |
| Keywords: | adult; cancer chemotherapy; controlled study; treatment outcome; treatment response; survival rate; retrospective studies; major clinical study; overall survival; fludarabine; allogeneic stem cell transplantation; clinical trial; paresthesia; drug efficacy; drug safety; cancer patient; follow up; phase 2 clinical trial; cohort analysis; recurrence; cyclophosphamide; retrospective study; acute lymphoblastic leukemia; age; multicenter study; graft versus host reaction; remission; recurrent disease; precursor cell lymphoblastic leukemia-lymphoma; bone marrow cell; phase 1 clinical trial; epidemiology; cytopenia; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; recurrence free survival; post hoc analysis; leukapheresis; inotuzumab ozogamicin; procedures; blinatumomab; humans; human; male; female; article; median survival time; car t-cell therapy; receptors, chimeric antigen; brexucabtagene autoleucel; kte-x19; b-precursor acute lymphoblastic leukemia; scholar-3; zuma-3; historically controlled study |
| Journal Title: | Journal of Hematology & Oncology |
| Volume: | 15 |
| ISSN: | 1756-8722 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2022-12-10 |
| Start Page: | 170 |
| Language: | English |
| DOI: | 10.1186/s13045-022-01379-0 |
| PUBMED: | 36494725 |
| PROVIDER: | scopus |
| PMCID: | PMC9734710 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 January 2023 -- Source: Scopus |
