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

91 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.

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

Fingerprint

Dive into the research topics of 'Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL'. Together they form a unique fingerprint.

Cite this