Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL

Regina M. Myers, Agne Taraseviciute, Seth M. Steinberg, Adam J. Lamble, Jennifer Sheppard, Bonnie Yates, Alexandra E. Kovach, Brent Wood, Michael J. Borowitz, Maryalice Stetler-Stevenson, Constance M. Yuan, Vinodh Pillai, Toni Foley, Perry Chung, Lee Chen, Daniel W. Lee, Colleen Annesley, Amanda DiNofia, Stephan A. Grupp, Samuel JohnDeepa Bhojwani, Patrick A. Brown, Theodore W Laetsch, Lia Gore, Rebecca A. Gardner, Susan R. Rheingold, Michael A. Pulsipher, Nirali N. Shah

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)932-944
Number of pages13
JournalJournal of Clinical Oncology
Volume40
Issue number9
DOIs
StatePublished - Mar 20 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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