TY - JOUR
T1 - Efficacy and Safety of Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T-Cell for the Treatment of Relapsed and Refractory AL Amyloidosis
AU - Lebel, Eyal
AU - Asherie, Nathalie
AU - Kfir-Erenfeld, Shlomit
AU - Grisariu, Sigal
AU - Avni, Batia
AU - Elias, Shlomo
AU - Assayag, Miri
AU - Dubnikov-Sharon, Tali
AU - Pick, Marjorie
AU - Alexander-Shani, Rivka
AU - Bessig, Nomi
AU - Herr, Shlomit
AU - Shehadeh, Alaa
AU - Ishtay, Aseel
AU - Pimienta, Shelly
AU - Vainstein, Vladimir
AU - Zimran, Eran
AU - Cohen, Yael
AU - Avivi, Irit
AU - Cohen, Cyrille
AU - Stepensky, Polina
AU - Gatt, Moshe E.
N1 - Publisher Copyright:
© 2024 by American Society of Clinical Oncology.
PY - 2025/6/10
Y1 - 2025/6/10
N2 - PURPOSEThe use of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy for AL amyloidosis (AL) is limited owing to patient frailty. HBI0101 anti-BCMA CART was the first proof of concept for its applicability to AL. This report addresses the AL patient cohort treated to date within the phase Ia/Ib clinical trial (ClinicalTrials.gov identifier: NCT04720313).METHODSAfter lymphodepletion, most AL patients were infused with 800 - 106 CARTs.RESULTSSixteen patients were treated, with a median of four previous lines of therapy (range, 3-10), 14/16 were triple class refractory, and 6/16 were refractory to belantamab. Most patients (13/16) had cardiac involvement, including five with MAYO stage IIIa/IIIb at study entry. Cytokine release syndrome was frequent (14/16) but mostly low grade (grade 3: 3/16, no grade 4/5). No neurologic toxicity or treatment-related deaths were observed. There were five grade 3 AL-related organ deteriorations resolved quickly with supportive care. The overall hematologic response rate was 15/16 (94%) and complete response (CR) was 12/16 (75%). Minimal residual disease negativity was achieved in 9/14 evaluable patients. Most patients (8/13 evaluable) achieved an objective organ response. Seven patients died during long-term follow-up, three while in CR/very good partial response, and the median overall survival was 10.1 months (95% CI, 5.8 to not reached).CONCLUSIONThis largest clinical trial of AL patients treated with anti-BCMA CART demonstrates acceptable and manageable toxicity in a highly frail and resistant population with remarkable efficacy, leading to fast organ responses. Among patients with baseline advanced cardiac disease, deaths in the first year were frequent, suggesting that this effective therapy should be considered earlier in the course of therapy. Anti-BCMA CART may become a powerful tool for improving organ function and survival in patients with AL.
AB - PURPOSEThe use of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy for AL amyloidosis (AL) is limited owing to patient frailty. HBI0101 anti-BCMA CART was the first proof of concept for its applicability to AL. This report addresses the AL patient cohort treated to date within the phase Ia/Ib clinical trial (ClinicalTrials.gov identifier: NCT04720313).METHODSAfter lymphodepletion, most AL patients were infused with 800 - 106 CARTs.RESULTSSixteen patients were treated, with a median of four previous lines of therapy (range, 3-10), 14/16 were triple class refractory, and 6/16 were refractory to belantamab. Most patients (13/16) had cardiac involvement, including five with MAYO stage IIIa/IIIb at study entry. Cytokine release syndrome was frequent (14/16) but mostly low grade (grade 3: 3/16, no grade 4/5). No neurologic toxicity or treatment-related deaths were observed. There were five grade 3 AL-related organ deteriorations resolved quickly with supportive care. The overall hematologic response rate was 15/16 (94%) and complete response (CR) was 12/16 (75%). Minimal residual disease negativity was achieved in 9/14 evaluable patients. Most patients (8/13 evaluable) achieved an objective organ response. Seven patients died during long-term follow-up, three while in CR/very good partial response, and the median overall survival was 10.1 months (95% CI, 5.8 to not reached).CONCLUSIONThis largest clinical trial of AL patients treated with anti-BCMA CART demonstrates acceptable and manageable toxicity in a highly frail and resistant population with remarkable efficacy, leading to fast organ responses. Among patients with baseline advanced cardiac disease, deaths in the first year were frequent, suggesting that this effective therapy should be considered earlier in the course of therapy. Anti-BCMA CART may become a powerful tool for improving organ function and survival in patients with AL.
UR - http://www.scopus.com/inward/record.url?scp=105008340650&partnerID=8YFLogxK
U2 - 10.1200/jco-24-02252
DO - 10.1200/jco-24-02252
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C2 - 39653116
AN - SCOPUS:105008340650
SN - 0732-183X
VL - 43
SP - 2007
EP - 2016
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 17
ER -