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 - 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.
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.
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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 -