Pilot Study of the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-BCMA (TNFRSF17) Specificity Humanized Conjugated With the Co-stimulatory Region 4-1BB and Signal-transduction CD3z (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma With Previous Treatment With Proteasome Inhibitor, Immunomodulatory Drug and Anti-CD38 Monoclonal Antibody

To assess the safety and efficacy of CARTBCMA ARI0002h in patients with relapsed/refractory multiple myeloma who have received treatment with proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

开始日期2020-05-27

申办/合作机构

Institut d'Investigacions Biomèdiques August Pi I Sunyer

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100 项与 Cesnicabtagene Autoleucel 相关的临床结果

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100 项与 Cesnicabtagene Autoleucel 相关的转化医学

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100 项与 Cesnicabtagene Autoleucel 相关的专利（医药）

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项与 Cesnicabtagene Autoleucel 相关的文献（医药）

2023-08-01·The Lancet. Oncology

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study.

Article

作者: Jiménez, Raquel ; Reguera, Juan Luis ; González-Calle, Verónica ; Oliver-Caldés, Aina ; Inogés, Susana ; López-Parra, Miriam ; Zabaleta, Aintzane ; Rodríguez-Otero, Paula ; Cabañas, Valentín ; Tovar, Natalia ; López-Corral, Lucía ; Varea, Sara ; Delgado, Julio ; López-Díaz de Cerio, Ascensión ; Olesti, Eulàlia ; Prósper, Felipe ; Pérez-Simón, José Antonio ; Martin-Antonio, Beatriz ; Fernández de Larrea, Carlos ; Urbano-Ispizua, Alvaro ; Calvo-Orteu, Maria ; Moraleda, José M ; Rodríguez-Lobato, Luis Gerardo ; Sáez-Peñataro, Joaquín ; Juan, Manel ; Paiva, Bruno ; Pascal, Mariona ; Español-Rego, Marta ; Sánchez-Salinas, Andrés ; Rosiñol, Laura ; Mateos, María-Victoria

BACKGROUNDChimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma.METHODSCARTBCMA-HCB-01 is a single-arm, multicentre study done in five academic centres in Spain. Eligible patients had relapsed or refractory multiple myeloma and were aged 18-75 years; with an Eastern Cooperative Oncology Group performance status of 0-2; two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; refractoriness to the last line of therapy; and measurable disease according to the International Myeloma Working Group criteria. Patients received an initial fractionated infusion of 3 × 10⁶ CAR T cells per kg bodyweight in three aliquots (0·3, 0·9, and 1·8 × 10⁶ CAR-positive cells per kg intravenously on days 0, 3, and 7) and a non-fractionated booster dose of up to 3 × 10⁶ CAR T cells per kg bodyweight, at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment. Here, we present an interim analysis of the ongoing trial; enrolment has ended. This study is registered with ClinicalTrials.gov, NCT04309981, and EudraCT, 2019-001472-11.FINDINGSBetween June 2, 2020, and Feb 24, 2021, 44 patients were assessed for eligibility, of whom 35 (80%) were enrolled. 30 (86%) of 35 patients received ARI0002h (median age 61 years [IQR 53-65], 12 [40%] were female, and 18 [60%] were male). At the planned interim analysis (cutoff date Oct 20, 2021), with a median follow-up of 12·1 months (IQR 9·1-13·5), overall response during the first 100 days from infusion was 100%, including 24 (80%) of 30 patients with a very good partial response or better (15 [50%] with complete response, nine [30%] with very good partial response, and six [20%] with partial response). Cytokine-release syndrome was observed in 24 (80%) of 30 patients (all grade 1-2). No cases of neurotoxic events were observed. Persistent grade 3-4 cytopenias were observed in 20 (67%) patients. Infections were reported in 20 (67%) patients. Three patients died: one because of progression, one because of a head injury, and one due to COVID-19.INTERPRETATIONARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach.FUNDINGInstituto de Salud Carlos III (co-funded by the EU), Fundación La Caixa, and Fundació Bosch i Aymerich.

British Journal of Haematology

Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T‐cells

Article

作者: Español‐Rego, Marta ; Reguera, Juan Luis ; Uribe‐Herranz, Mireia ; Pascal, Mariona ; Benítez‐Ribas, Daniel ; Puig, Noemí ; Inogés, Susana ; Tréboles, Karen ; Fernández de Larrea, Carlos ; Urbano‐Ispizua, Álvaro ; López‐Diaz de Cerio, Ascensión ; Cabañas, Valentín ; Tovar, Natalia ; Aróstegui, Juan Ignacio ; Agulló, Cristina ; Moraleda, José María ; Zabaleta, Aintzane ; Zugasti, Inés ; Mora, Génesis ; Ortiz de Landazuri, Iñaki ; Paiva, Bruno ; Rodríguez Otero, Paula ; Contreras, María Teresa ; Rodríguez‐Lobato, Luis Gerardo ; González‐Calle, Verónica ; González, Europa Azucena ; Juan, Manel ; Navarro, Sergio ; Martin‐Antonio, Beatriz ; Mateos, María Victoria ; Oliver‐Caldés, Aina ; Rosiñol, Laura ; Yagüe, Jordi ; Charry, Paola

SummaryChimeric antigen receptor (CAR) T‐cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M‐protein. Quantitative immunoprecipitation mass spectrometry (QIP‐MS) can accurately measure serum M‐protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies. Here, we investigate the outcome of QIP‐MS in 33 patients treated with the academic BCMA‐directed CAR T‐cell ARI0002h (Cesnicabtagene Autoleucel). QIP‐MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M‐proteins and minor additional peaks. Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP‐MS showed a high global concordance (78.8%) with sIFE, whereas it was only moderate (55.6%) with bone marrow (BM)‐based next‐generation flow cytometry (NGF). Furthermore, QIP‐MS consistently demonstrated the lowest negativity rate across the different timepoints (27.3% vs. 60.0% in months 1 and 12, respectively). Patients with QIP‐MS(+)/BM‐based NGF(−) showed a non‐significant shorter median progression free survival than those with QIP‐MS(−)/BM‐based NGF(−). In summary, we show the first experience to our knowledge demonstrating that QIP‐MS could be particularly useful as a non‐invasive technique when evaluating response after CAR T‐cell treatment in MM.

100 项与 Cesnicabtagene Autoleucel 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
浆细胞骨髓瘤难治	临床2期	西班牙	Instituto De SAlud Carlos Iii De Madrid	2020-05-27
复发性多发性骨髓瘤	临床2期	西班牙	Instituto De SAlud Carlos Iii De Madrid	2020-05-27

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EHA2024	N/A	多发性骨髓瘤 sBCMA \| circulating EVs	19	PHE885	憲繭鬱壓壓鬱壓簾齋願(積齋鹹構鬱憲鑰選膚憲) = The presence of BCMA was observed and quantified in circulating EVs (these EVs were characterized by canonical EV-associated proteins). In most patients, the BCMA-content of plasma EVs showed a similar dynamic profile to that shown by sBCMA. 鹹膚憲選窪簾遞顧製顧 (夢衊鏇網窪鏇製簾膚廠 ) 更多	-	2024-05-14
EHA2024	N/A	多发性骨髓瘤 sBCMA \| circulating EVs	19	ARI0002h		-	2024-05-14
NCT04309981 (CARTBCMA-HCB-01, ASH2023)	临床1/2期	复发性多发性骨髓瘤	60	ARI0002h	(鏇選壓窪繭獵範醖膚膚) = 憲鏇簾憲鑰鑰廠願憲製憲觸選簾壓蓋淵繭網窪 (網鏇鹽製觸積夢簾積範 ) 更多	-	2023-12-11
NCT04309981 (CARTBCMA-HCB-01, Pubmed)	临床1/2期	浆细胞骨髓瘤难治	35	ARI0002h	(夢鬱餘鏇糧遞積餘獵選) = 遞膚簾積網鹹築餘衊選獵範醖鹽顧廠鹹廠築鹽 (鹹憲簾淵繭糧鹹繭憲顧 ) 更多	-	2023-07-03
NCT04309981 (CARTBCMA-HCB-01, EHA2022) 人工标引	临床1/2期	复发性多发性骨髓瘤	35	Cyclophosphamide+fludarabine+ARI0002H	(艱壓餘蓋願繭鬱衊窪鏇) = 製繭築願願獵繭網鑰廠衊廠衊醖簾窪廠鹹構遞 (構鹽築鹽鏇襯鏇糧鬱憲 ) 更多	积极	2022-05-12
NCT04309981 (CARTBCMA-HCB-01, ASH2021) 人工标引	临床1/2期	复发性多发性骨髓瘤	35	ARI0002h	(膚繭遞鹹選範鏇鏇艱觸) = 餘膚糧繭繭範膚蓋鹹選簾膚觸糧選鹹鑰窪獵網 (獵衊窪蓋選構襯積襯襯 ) 更多	积极	2021-11-05