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Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies.
Cohen, Adam D; Parekh, Samir; Santomasso, Bianca D; Gállego Pérez-Larraya, Jaime; van de Donk, Niels W C J; Arnulf, Bertrand; Mateos, Maria-Victoria; Lendvai, Nikoletta; Jackson, Carolyn C; De Braganca, Kevin C; Schecter, Jordan M; Marquez, Loreta; Lee, Erin; Cornax, Ingrid; Zudaire, Enrique; Li, Claire; Olyslager, Yunsi; Madduri, Deepu; Varsos, Helen; Pacaud, Lida; Akram, Muhammad; Geng, Dong; Jakubowiak, Andrzej; Einsele, Hermann; Jagannath, Sundar.
Afiliación
  • Cohen AD; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Parekh S; Mount Sinai Medical Center, New York, NY, USA.
  • Santomasso BD; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Gállego Pérez-Larraya J; Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain.
  • van de Donk NWCJ; Department of Hematology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Arnulf B; Hôpital Saint Louis, Paris, France.
  • Mateos MV; University Hospital of Salamanca/Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
  • Lendvai N; Janssen R&D, Raritan, NJ, USA.
  • Jackson CC; Janssen R&D, Raritan, NJ, USA.
  • De Braganca KC; Janssen R&D, Raritan, NJ, USA.
  • Schecter JM; Janssen R&D, Raritan, NJ, USA.
  • Marquez L; Janssen R&D, Raritan, NJ, USA.
  • Lee E; Janssen R&D, Raritan, NJ, USA.
  • Cornax I; Janssen R&D, Raritan, NJ, USA.
  • Zudaire E; Janssen R&D, Spring House, PA, USA.
  • Li C; Janssen R&D, Spring House, PA, USA.
  • Olyslager Y; Janssen R&D, Beerse, Belgium.
  • Madduri D; Janssen R&D, Raritan, NJ, USA.
  • Varsos H; Janssen R&D, Raritan, NJ, USA.
  • Pacaud L; Legend Biotech USA, Inc, Piscataway, NJ, USA.
  • Akram M; Legend Biotech USA, Inc, Piscataway, NJ, USA.
  • Geng D; Legend Biotech USA, Inc, Piscataway, NJ, USA.
  • Jakubowiak A; University of Chicago, Chicago, IL, USA.
  • Einsele H; Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany.
  • Jagannath S; Mount Sinai Medical Center, New York, NY, USA. sundar.jagannath@mountsinai.org.
Blood Cancer J ; 12(2): 32, 2022 02 24.
Article en En | MEDLINE | ID: mdl-35210399
Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit-risk profile for treatment of MM.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de Neurotoxicidad / Receptores Quiméricos de Antígenos / Mieloma Múltiple Tipo de estudio: Etiology_studies / Incidence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Cancer J Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de Neurotoxicidad / Receptores Quiméricos de Antígenos / Mieloma Múltiple Tipo de estudio: Etiology_studies / Incidence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Cancer J Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos