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Frey, Noelle V.; Shaw, Pamela A.; Hexner, Elizabeth O.; Pequignot, Edward; Gill, Saar; Luger, Selina M.; Mangan, James K.; Loren, Alison W.; Perl, Alexander E.; Maude, Shannon L.; Grupp, Stephan A.; Shah, Nirav N.; Gilmore, Joan; Lacey, Simon F.; Melenhorst, Jos J.; Levine, Bruce L.; June, Carl H.; Porter, David L.

Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia

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  • Medientyp: E-Artikel
  • Titel: Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia
  • Beteiligte: Frey, Noelle V.; Shaw, Pamela A.; Hexner, Elizabeth O.; Pequignot, Edward; Gill, Saar; Luger, Selina M.; Mangan, James K.; Loren, Alison W.; Perl, Alexander E.; Maude, Shannon L.; Grupp, Stephan A.; Shah, Nirav N.; Gilmore, Joan; Lacey, Simon F.; Melenhorst, Jos J.; Levine, Bruce L.; June, Carl H.; Porter, David L.
  • Erschienen: American Society of Clinical Oncology (ASCO), 2020
  • Erschienen in: Journal of Clinical Oncology
  • Sprache: Englisch
  • DOI: 10.1200/jco.19.01892
  • ISSN: 0732-183X; 1527-7755
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>PURPOSE</jats:title><jats:p> The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel (CTL019) has an 81% response rate in children with relapsed or chemotherapy refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is a life-threatening treatment-related toxicity that limits the full therapeutic potential in adults. We report outcomes for adults with r/r ALL treated with an optimized CTL019 dosing and CRS management strategy. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> Adults with r/r B-cell ALL received CTL019 in 1 of 2 trials. Patients received lymphodepletion followed by CTL019 as either a one-time infusion or fractionated infusions split over 3 days (day 1, 10%; day 2, 30%; day 3, 60%), which allowed for day 2 and day 3 doses to be held for early CRS. Total planned CTL019 dose varied with adaptive protocol modifications in response to efficacy and CRS toxicity. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Thirty-five adults with r/r ALL received CTL019 in 1 of 3 dosing cohorts. The low-dose cohort (n = 9) received single or fractionated dosing and had manageable toxicity with a 33% complete remission (CR) rate. In the high-dose single infusion cohort, 3 of 6 patients with refractory CRS concurrent with culture-positive sepsis died, and 3 achieved CR. The 20 patients in the high-dose fractionated (HDF) cohort had a 90% CR rate and manageable CRS. The HDF cohort had the highest survival, with a 2-year overall survival of 73% (95% CI, 46% to 88%) and event-free survival of 49.5% (95% CI, 21% to 73%). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Fractionated dosing of CTL019 with intrapatient dose modification optimizes safety without compromising efficacy in adults with r/r ALL. </jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang