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Smith, Eric L.; Mailankody, Sham; Staehr, Mette; Wang, Xiuyan; Senechal, Brigitte; Purdon, Terence J.; Daniyan, Anthony F.; Geyer, Mark B.; Goldberg, Aaron D.; Mead, Elena; Santomasso, Bianca D.; Landa, Jonathan; Rimner, Andreas; Riviere, Isabelle; Landgren, Ola; Brentjens, Renier J.

BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy

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  • Medientyp: E-Artikel
  • Titel: BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy
  • Beteiligte: Smith, Eric L.; Mailankody, Sham; Staehr, Mette; Wang, Xiuyan; Senechal, Brigitte; Purdon, Terence J.; Daniyan, Anthony F.; Geyer, Mark B.; Goldberg, Aaron D.; Mead, Elena; Santomasso, Bianca D.; Landa, Jonathan; Rimner, Andreas; Riviere, Isabelle; Landgren, Ola; Brentjens, Renier J.
  • Erschienen: American Association for Cancer Research (AACR), 2019
  • Erschienen in: Cancer Immunology Research
  • Sprache: Englisch
  • DOI: 10.1158/2326-6066.cir-18-0551
  • ISSN: 2326-6066; 2326-6074
  • Schlagwörter: Cancer Research ; Immunology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>We present a case of a patient with multiply relapsed, refractory myeloma whose clinical course showed evidence of a synergistic abscopal-like response to chimeric antigen receptor (CAR) T-cell therapy and localized radiotherapy (XRT). Shortly after receiving B-cell maturation antigen (BCMA)–targeted CAR T-cell therapy, the patient required urgent high-dose steroids and XRT for spinal cord compression. Despite the steroids, the patient had a durable systemic response that could not be attributed to XRT alone. Post-XRT findings included a second wave of fever and increased CRP and IL6, beginning 21 days after CAR T cells, which is late for cytokine-release syndrome from CAR T-cell therapy alone on this trial. Given this response, which resembled cytokine-release syndrome, immediately following XRT, we investigated changes in the patient's T-cell receptor (TCR) repertoire over 10 serial time points. Comparing T-cell diversity via Morisita's overlap indices (CD), we discovered that, although the diversity was initially stable after CAR T-cell therapy compared with baseline (CD = 0.89–0.97, baseline vs. 4 time points after CAR T cells), T-cell diversity changed after the conclusion of XRT, with &amp;gt;30% newly expanded TCRs (CD = 0.56–0.69, baseline vs. 4 time points after XRT). These findings suggest potential synergy between radiation and CAR T-cell therapies resulting in an abscopal-like response.</jats:p>
  • Zugangsstatus: Freier Zugang