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Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL.
Myers, Regina M; Taraseviciute, Agne; Steinberg, Seth M; Lamble, Adam J; Sheppard, Jennifer; Yates, Bonnie; Kovach, Alexandra E; Wood, Brent; Borowitz, Michael J; Stetler-Stevenson, Maryalice; Yuan, Constance M; Pillai, Vinodh; Foley, Toni; Chung, Perry; Chen, Lee; Lee, Daniel W; Annesley, Colleen; DiNofia, Amanda; Grupp, Stephan A; John, Samuel; Bhojwani, Deepa; Brown, Patrick A; Laetsch, Theodore W; Gore, Lia; Gardner, Rebecca A; Rheingold, Susan R; Pulsipher, Michael A; Shah, Nirali N.
Afiliação
  • Myers RM; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • Taraseviciute A; Section of Transplantation and Cellular Therapy, Children's Hospital Los Angeles Cancer and Blood Disease Institute, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Steinberg SM; Current affiliation: Janssen Research & Development, LLC, Raritan, NJ.
  • Lamble AJ; Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Sheppard J; Division of Hematology and Oncology University of Washington, Seattle Children's Hospital, Seattle, WA.
  • Yates B; Division of Pediatric Hematology-Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
  • Kovach AE; National Cancer Institute/Center for Cancer Research, Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD.
  • Wood B; Section of Transplantation and Cellular Therapy, Children's Hospital Los Angeles Cancer and Blood Disease Institute, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Borowitz MJ; Section of Transplantation and Cellular Therapy, Children's Hospital Los Angeles Cancer and Blood Disease Institute, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Stetler-Stevenson M; Department of Pathology, Johns Hopkins Hospital, Baltimore, MD.
  • Yuan CM; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Pillai V; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • Foley T; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • Chung P; National Cancer Institute/Center for Cancer Research, Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD.
  • Chen L; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • Lee DW; Section of Transplantation and Cellular Therapy, Children's Hospital Los Angeles Cancer and Blood Disease Institute, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Annesley C; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA.
  • DiNofia A; Division of Hematology and Oncology University of Washington, Seattle Children's Hospital, Seattle, WA.
  • Grupp SA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • John S; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • Bhojwani D; Division of Pediatric Hematology-Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
  • Brown PA; Division of Hematology/Oncology, Children's Hospital Los Angeles Cancer and Blood Disease Institute, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Laetsch TW; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
  • Gore L; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • Gardner RA; Division of Pediatric Hematology-Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX.
  • Rheingold SR; Pediatric Heme/Onc/BMT-CT, University of Colorado, Children's Hospital Colorado, Aurora, CO.
  • Pulsipher MA; Division of Hematology and Oncology University of Washington, Seattle Children's Hospital, Seattle, WA.
  • Shah NN; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.
J Clin Oncol ; 40(9): 932-944, 2022 03 20.
Article em En | MEDLINE | ID: mdl-34767461
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-naïve patients. Among patients evaluable for CD19-CAR response (n = 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 blinatumomab-naïve 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 = .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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Anticorpos Biespecíficos / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Adult / Child / Humans Idioma: En Revista: J Clin Oncol Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Anticorpos Biespecíficos / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Adult / Child / Humans Idioma: En Revista: J Clin Oncol Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos