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

Bijal D. Shah; Armin Ghobadi; Olalekan O. Oluwole; Aaron C. Logan; Nicolas Boissel; Ryan D. Cassaday; Thibaut Leguay; Michael R. Bishop; Max S. Topp; Dimitrios Tzachanis; Kristen M. O’Dwyer; Martha L. Arellano; Yi Lin; Maria R. Baer; Gary J. Schiller; Jae H. Park; Marion Subklewe; Mehrdad Abedi; Monique C. Minnema; William G. Wierda; Daniel J. DeAngelo; Patrick Stiff; Deepa Jeyakumar; Jinghui Dong; Sabina Adhikary; Lang Zhou; Petra C. Schuberth; Imi Faghmous; Behzad Kharabi Masouleh; Roch Houot

doi:10.1186/s13045-022-01379-0

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

Bijal D. Shah, Armin Ghobadi, Olalekan O. Oluwole, Aaron C. Logan, Nicolas Boissel, Ryan D. Cassaday, Thibaut Leguay, Michael R. Bishop, Max S. Topp, Dimitrios Tzachanis, Kristen M. O’Dwyer, Martha L. Arellano, Yi Lin, Maria R. Baer, Gary J. Schiller, Jae H. Park, Marion Subklewe, Mehrdad Abedi, Monique C. Minnema, William G. WierdaDaniel J. DeAngelo, Patrick Stiff, Deepa Jeyakumar, Jinghui Dong, Sabina Adhikary, Lang Zhou, Petra C. Schuberth, Imi Faghmous, Behzad Kharabi Masouleh, Roch Houot

Hematology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	170
Journal	Journal of Hematology and Oncology
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s13045-022-01379-0
State	Published - Dec 2022

Keywords

B-precursor acute lymphoblastic leukemia
Brexucabtagene autoleucel
CAR T-cell therapy
KTE-X19
SCHOLAR-3
ZUMA-3

ASJC Scopus subject areas

Molecular Biology
Hematology
Oncology
Cancer Research

Access to Document

10.1186/s13045-022-01379-0

Cite this

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., ... Houot, R. (2022). 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 of Hematology and Oncology, 15(1), Article 170. https://doi.org/10.1186/s13045-022-01379-0

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. / Shah, Bijal D.; Ghobadi, Armin; Oluwole, Olalekan O. et al.
In: Journal of Hematology and Oncology, Vol. 15, No. 1, 170, 12.2022.

Research output: Contribution to journal › Article › peer-review

Shah, BD, Ghobadi, A, Oluwole, OO, Logan, AC, Boissel, N, Cassaday, RD, Leguay, T, Bishop, MR, Topp, MS, Tzachanis, D, O’Dwyer, KM, Arellano, ML, Lin, Y, Baer, MR, Schiller, GJ, Park, JH, Subklewe, M, Abedi, M, Minnema, MC, Wierda, WG, DeAngelo, DJ, Stiff, P, Jeyakumar, D, Dong, J, Adhikary, S, Zhou, L, Schuberth, PC, Faghmous, I, Masouleh, BK & Houot, R 2022, '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 of Hematology and Oncology, vol. 15, no. 1, 170. https://doi.org/10.1186/s13045-022-01379-0

@article{29ef38bb35e348009522f2f4cec339aa,

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.",

keywords = "B-precursor acute lymphoblastic leukemia, Brexucabtagene autoleucel, CAR T-cell therapy, KTE-X19, SCHOLAR-3, ZUMA-3",

author = "Shah, {Bijal D.} and Armin Ghobadi and Oluwole, {Olalekan O.} and Logan, {Aaron C.} and Nicolas Boissel and Cassaday, {Ryan D.} and Thibaut Leguay and Bishop, {Michael R.} and Topp, {Max S.} and Dimitrios Tzachanis and O{\textquoteright}Dwyer, {Kristen M.} and Arellano, {Martha L.} and Yi Lin and Baer, {Maria R.} and Schiller, {Gary J.} and Park, {Jae H.} and Marion Subklewe and Mehrdad Abedi and Minnema, {Monique C.} and Wierda, {William G.} and DeAngelo, {Daniel J.} and Patrick Stiff and Deepa Jeyakumar and Jinghui Dong and Sabina Adhikary and Lang Zhou and Schuberth, {Petra C.} and Imi Faghmous and Masouleh, {Behzad Kharabi} and Roch Houot",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13045-022-01379-0",

language = "English (US)",

volume = "15",

journal = "Journal of Hematology and Oncology",

issn = "1756-8722",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - 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

AU - Shah, Bijal D.

AU - Ghobadi, Armin

AU - Oluwole, Olalekan O.

AU - Logan, Aaron C.

AU - Boissel, Nicolas

AU - Cassaday, Ryan D.

AU - Leguay, Thibaut

AU - Bishop, Michael R.

AU - Topp, Max S.

AU - Tzachanis, Dimitrios

AU - O’Dwyer, Kristen M.

AU - Arellano, Martha L.

AU - Lin, Yi

AU - Baer, Maria R.

AU - Schiller, Gary J.

AU - Park, Jae H.

AU - Subklewe, Marion

AU - Abedi, Mehrdad

AU - Minnema, Monique C.

AU - Wierda, William G.

AU - DeAngelo, Daniel J.

AU - Stiff, Patrick

AU - Jeyakumar, Deepa

AU - Dong, Jinghui

AU - Adhikary, Sabina

AU - Zhou, Lang

AU - Schuberth, Petra C.

AU - Faghmous, Imi

AU - Masouleh, Behzad Kharabi

AU - Houot, Roch

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - B-precursor acute lymphoblastic leukemia

KW - Brexucabtagene autoleucel

KW - CAR T-cell therapy

KW - KTE-X19

KW - SCHOLAR-3

KW - ZUMA-3

UR - http://www.scopus.com/inward/record.url?scp=85143678459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85143678459&partnerID=8YFLogxK

U2 - 10.1186/s13045-022-01379-0

DO - 10.1186/s13045-022-01379-0

M3 - Article

C2 - 36494725

AN - SCOPUS:85143678459

SN - 1756-8722

VL - 15

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

IS - 1

M1 - 170

ER -

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

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this