TY - JOUR
T1 - Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells
AU - Lamble, Adam J.
AU - Myers, Regina M.
AU - Taraseviciute, Agne
AU - John, Samuel
AU - Yates, Bonnie
AU - Steinberg, Seth M.
AU - Sheppard, Jennifer
AU - Kovach, Alexandra E.
AU - Wood, Brent
AU - Borowitz, Michael J.
AU - Stetler-Stevenson, Maryalice
AU - Yuan, Constance M.
AU - Pillai, Vinodh
AU - Foley, Toni
AU - Chung, Perry
AU - Chen, Lee
AU - Lee, Daniel W.
AU - Annesley, Colleen
AU - DiNofia, Amanda
AU - Grupp, Stephan A.
AU - Verneris, Michael R.
AU - Gore, Lia
AU - Laetsch, Theodore W.
AU - Bhojwani, Deepa
AU - Brown, Patrick A.
AU - Pulsipher, Michael A.
AU - Rheingold, Susan R.
AU - Gardner, Rebecca A.
AU - Shah, Nirali N.
N1 - Publisher Copyright:
© 2023 American Society of Hematology. All rights reserved.
PY - 2023/2/28
Y1 - 2023/2/28
N2 - Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize preinfusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 patients treated with CAR, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. A greater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high preinfusion disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only preinfusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI, 9-17) and was particularly dismal in patients experiencing an LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplantation, is critical and warrants further investigation on prospective clinical trials.
AB - Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize preinfusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 patients treated with CAR, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. A greater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high preinfusion disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only preinfusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI, 9-17) and was particularly dismal in patients experiencing an LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplantation, is critical and warrants further investigation on prospective clinical trials.
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UR - http://www.scopus.com/inward/citedby.url?scp=85146295810&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2022007423
DO - 10.1182/bloodadvances.2022007423
M3 - Article
C2 - 35482927
AN - SCOPUS:85146295810
SN - 2473-9529
VL - 7
SP - 575
EP - 585
JO - Blood Advances
JF - Blood Advances
IS - 4
ER -