TY - JOUR
T1 - Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL
AU - Myers, Regina M.
AU - Taraseviciute, Agne
AU - Steinberg, Seth M.
AU - Lamble, Adam J.
AU - Sheppard, Jennifer
AU - Yates, Bonnie
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 - John, Samuel
AU - Bhojwani, Deepa
AU - Brown, Patrick A.
AU - Laetsch, Theodore W
AU - Gore, Lia
AU - Gardner, Rebecca A.
AU - Rheingold, Susan R.
AU - Pulsipher, Michael A.
AU - Shah, Nirali N.
N1 - Funding Information:
Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and the Warren Grant Magnuson Clinical Center (ZIA BC 011823, N.N.S.).
Publisher Copyright:
© 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2022/3/20
Y1 - 2022/3/20
N2 - PURPOSE CD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes. PATIENTS AND METHODS We conducted a multicenter, retrospective review of children and young adults with relapsed or refractory ALL who received CD19-CAR between 2012 and 2019. Primary objectives addressed 6-month relapse-free survival (RFS) and event-free survival (EFS), stratified by blinatumomab use. Secondary objectives included comparison of longer-term survival outcomes, complete remission rates, CD19 modulation, and identification of factors associated with EFS. RESULTS Of 420 patients (median age, 12.7 years; interquartile range, 7.1-17.5) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR constructs, 77 (18.3%) received prior blinatumomab. Blinatumomab-exposed patients more frequently harbored KMT2A rearrangements and underwent a prior stem-cell transplant than blinatumomab-naive patients. Among patients evaluable for CD19-CAR response (n 5 412), blinatumomab nonresponders had lower complete remission rates to CD19-CAR (20 of 31, 64.5%) than blinatumomab responders (39 of 42, 92.9%) or blinatumomab-naive patients (317 of 339, 93.5%), P, .0001. Following CD19-CAR, blinatumomab nonresponders had worse 6-month EFS (27.3%; 95% CI, 13.6 to 43.0) compared with blinatumomab responders (66.9%; 95% CI, 50.6 to 78.9; P,.0001) or blinatumomabnaive patients (72.6%; 95% CI, 67.5 to 77; P , .0001) and worse RFS. High-disease burden independently associated with inferior EFS. CD19-dim or partial expression (preinfusion) was more frequently seen in blinatumomab-exposed patients (13.3% v 6.5%; P 5 .06) and associated with lower EFS and RFS. CONCLUSION With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high-disease burden were independently associated with worse RFS and EFS, identifying important indicators of long-term outcomes following CD19-CAR
AB - PURPOSE CD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes. PATIENTS AND METHODS We conducted a multicenter, retrospective review of children and young adults with relapsed or refractory ALL who received CD19-CAR between 2012 and 2019. Primary objectives addressed 6-month relapse-free survival (RFS) and event-free survival (EFS), stratified by blinatumomab use. Secondary objectives included comparison of longer-term survival outcomes, complete remission rates, CD19 modulation, and identification of factors associated with EFS. RESULTS Of 420 patients (median age, 12.7 years; interquartile range, 7.1-17.5) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR constructs, 77 (18.3%) received prior blinatumomab. Blinatumomab-exposed patients more frequently harbored KMT2A rearrangements and underwent a prior stem-cell transplant than blinatumomab-naive patients. Among patients evaluable for CD19-CAR response (n 5 412), blinatumomab nonresponders had lower complete remission rates to CD19-CAR (20 of 31, 64.5%) than blinatumomab responders (39 of 42, 92.9%) or blinatumomab-naive patients (317 of 339, 93.5%), P, .0001. Following CD19-CAR, blinatumomab nonresponders had worse 6-month EFS (27.3%; 95% CI, 13.6 to 43.0) compared with blinatumomab responders (66.9%; 95% CI, 50.6 to 78.9; P,.0001) or blinatumomabnaive patients (72.6%; 95% CI, 67.5 to 77; P , .0001) and worse RFS. High-disease burden independently associated with inferior EFS. CD19-dim or partial expression (preinfusion) was more frequently seen in blinatumomab-exposed patients (13.3% v 6.5%; P 5 .06) and associated with lower EFS and RFS. CONCLUSION With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high-disease burden were independently associated with worse RFS and EFS, identifying important indicators of long-term outcomes following CD19-CAR
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U2 - 10.1200/JCO.21.01405
DO - 10.1200/JCO.21.01405
M3 - Article
C2 - 34767461
AN - SCOPUS:85119926391
SN - 0732-183X
VL - 40
SP - 932
EP - 944
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -