Lebel Eyal, Asherie Nathalie, Kfir-Erenfeld Shlomit, Grisariu Sigal, Avni Batia, Elias Shlomo, Assayag Miri, Dubnikov-Sharon Tali, Pick Marjorie, Alexander-Shani Rivka, Bessig Nomi, Herr Shlomit, Shehadeh Alaa, Ishtay Aseel, Pimienta Shelly, Vainstein Vladimir, Zimran Eran, Cohen Yael, Avivi Irit, Cohen Cyrille, Stepensky Polina, Gatt Moshe E
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
J Clin Oncol. 2024 Dec 9:JCO2402252. doi: 10.1200/JCO-24-02252.
The 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).
After lymphodepletion, most AL patients were infused with 800 × 10 CARTs.
Sixteen 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).
This 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.
由于患者身体虚弱，抗B细胞成熟抗原（BCMA）嵌合抗原受体T细胞（CART）疗法在治疗AL淀粉样变性（AL）中的应用受到限制。HBI0101抗BCMA CART是其适用于AL的首个概念验证。本报告阐述了在Ia/Ib期临床试验（ClinicalTrials.gov标识符：NCT04720313）中至今接受治疗的AL患者队列。
在淋巴细胞清除后，大多数AL患者输注了800×10的CART细胞。
16例患者接受了治疗，既往治疗的中位数为4线（范围3 - 10线），14/16例为三联难治性，6/16例对贝利妥昔单抗难治。大多数患者（13/16）有心脏受累，其中5例在研究入组时处于MAYO IIIa/IIIb期。细胞因子释放综合征很常见（14/16），但大多为低级别（3级：3/16，无4/5级）。未观察到神经毒性或治疗相关死亡。有5例3级AL相关器官恶化通过支持治疗迅速缓解。总体血液学缓解率为15/16（94%），完全缓解（CR）为12/16（75%）。9/14例可评估患者实现了微小残留病阴性。大多数患者（8/13例可评估）实现了客观器官反应。7例患者在长期随访期间死亡，3例在CR/非常好的部分缓解期死亡，总体生存中位数为10.1个月（95%CI，5.8至未达到）。
这项抗BCMA CART治疗AL患者的最大规模临床试验表明，在高度虚弱和耐药的人群中，毒性是可接受且可控的，疗效显著，可导致快速的器官反应。在基线有晚期心脏疾病的患者中，第一年死亡频繁，这表明应在治疗过程中更早地考虑这种有效疗法。抗BCMA CART可能成为改善AL患者器官功能和生存的有力工具。
