TY - JOUR
T1 - Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies
AU - Cohen, Adam D.
AU - Parekh, Samir
AU - Santomasso, Bianca D.
AU - Pérez-Larraya, Jaime Gállego
AU - van de Donk, Niels W.C.J.
AU - Arnulf, Bertrand
AU - Mateos, Maria Victoria
AU - Lendvai, Nikoletta
AU - Jackson, Carolyn C.
AU - De Braganca, Kevin C.
AU - Schecter, Jordan M.
AU - Marquez, Loreta
AU - Lee, Erin
AU - Cornax, Ingrid
AU - Zudaire, Enrique
AU - Li, Claire
AU - Olyslager, Yunsi
AU - Madduri, Deepu
AU - Varsos, Helen
AU - Pacaud, Lida
AU - Akram, Muhammad
AU - Geng, Dong
AU - Jakubowiak, Andrzej
AU - Einsele, Hermann
AU - Jagannath, Sundar
N1 - Funding Information:
This study was funded by Janssen Research & Development, LLC and Legend Biotech, Inc. Medical writing support was provided by Jaya Kolipaka of Eloquent Scientific Solutions, and funded by Janssen Global Services, LLC. The authors thank the patients who participated in the study and their families and caregivers, the physicians and nurses who cared for patients and supported this clinical trial, the staff members at the study sites, and the staff members involved in data collection and analyses.
Funding Information:
This study was funded by Janssen Research & Development, LLC and Legend Biotech, Inc. Medical writing support was provided by Jaya Kolipaka of Eloquent Scientific Solutions, and funded by Janssen Global Services, LLC. The authors thank the patients who participated in the study and their families and caregivers, the physicians and nurses who cared for patients and supported this clinical trial, the staff members at the study sites, and the staff members involved in data collection and analyses.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85125330491&partnerID=8YFLogxK
U2 - 10.1038/s41408-022-00629-1
DO - 10.1038/s41408-022-00629-1
M3 - Article
C2 - 35210399
AN - SCOPUS:85125330491
SN - 2044-5385
VL - 12
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 2
M1 - 32
ER -