Pub Date : 2025-01-09DOI: 10.1182/blood.2024026030
Anisha Elizabeth Jacob, Girish Venkataraman
{"title":"CD123 to the rescue.","authors":"Anisha Elizabeth Jacob, Girish Venkataraman","doi":"10.1182/blood.2024026030","DOIUrl":"https://doi.org/10.1182/blood.2024026030","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 2","pages":"248"},"PeriodicalIF":21.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-09DOI: 10.1182/blood.2024025699
Gloria Iacoboni, Franck Morschhauser
Abstract: Follicular lymphoma (FL) usually requires multiple lines of therapy, and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell-redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.
{"title":"Building the future management of follicular lymphoma with T-cell-redirecting strategies.","authors":"Gloria Iacoboni, Franck Morschhauser","doi":"10.1182/blood.2024025699","DOIUrl":"10.1182/blood.2024025699","url":null,"abstract":"<p><strong>Abstract: </strong>Follicular lymphoma (FL) usually requires multiple lines of therapy, and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell-redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"170-175"},"PeriodicalIF":21.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-09DOI: 10.1182/blood.2024025987
Jan Eckmann, Tanja Fauti, Marlene Biehl, Aintzane Zabaleta, Laura Blanco, Iva Lelios, Stefan Gottwald, Richard Rae, Stefanie Lechner, Christa Bayer, Quincy Dekempe, Franz Osl, Nadege Carrié, Sahar Kassem, Stefan Lorenz, Tony Christopeit, Alejandro Carpy, Alexander Bujotzek, Ann-Marie Bröske, Iryna Dekhtiarenko, Jan Attig, Leo Kunz, Floriana Cremasco, Roberto Adelfio, Georg Fertig, Stefan Dengl, Christian Gassner, Felix Bormann, Claudia Kirstenpfad, Thomas Kraft, Sarah Diggelmann, Melanie Knobloch, Carina Hage, Romi Feddersen, Gordon Heidkamp, Thomas Pöschinger, Maud Mayoux, Luise Bernasconi, Felipe Prosper, Charles Dumontet, Ludovic Martinet, Stéphane Leclair, Wei Xu, Bruno Paiva, Christian Klein, Pablo Umaña
Abstract: Despite several approved therapies, multiple myeloma (MM) remains an incurable disease with high unmet medical need. "Off-the-shelf" T-cell bispecific antibodies (TCBs) targeting B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) have demonstrated high objective response rates in heavily pretreated patients with MM; however, primary resistance, short duration of response, and relapse driven by antigen shift frequently occur. Although GPRC5D represents the most selective target in MM, recent findings indicate antigen loss occurs more frequently than with BCMA. Thus, anti-GPRC5D immunotherapies must hit hard during a short period of time. Here, we characterize forimtamig, a novel GPRC5D-targeting TCB with 2+1 format. Bivalent binding of forimtamig to GPRC5D confers higher affinity than classical 1+1 TCB formats correlating with formation of more stable immunological synapses and higher potency in tumor cell killing and T-cell activation. Using an orthotopic mouse model of MM, forimtamig recruited T effector cells to the bone marrow and induced rapid tumor killing even after the introduction of step-up dosing to mitigate cytokine release. Combination of forimtamig with standard-of-care agents including anti-CD38 antibodies, immunomodulatory drugs, and proteasome inhibitors improved depth and duration of response. The combination of forimtamig with novel therapeutic agents including BCMA TCB and cereblon E3 ligase modulatory drugs was potent and prevented occurrence of GPRC5D -negative tumor relapse. Forimtamig is currently being evaluated in phase 1 clinical trials in patients with relapsed and refractory MM for monotherapy and in combination treatments. This trial was registered at www.ClinicalTrials.gov as #NCT04557150.
尽管有多种疗法获得批准，但多发性骨髓瘤（MM）仍是一种无法治愈的疾病，有大量医疗需求尚未得到满足。以 BCMA 和 GPRC5D 为靶点的 "现成 "T 细胞双特异性抗体（TCBs）已在接受过大量预处理的 MM 患者中显示出较高的客观反应率（ORR），但由于抗原转移而导致的原发性耐药、反应持续时间短和复发的情况时有发生。虽然 GPRC5D 是 MM 中最具选择性的靶点，但最近的研究结果表明，抗原丢失比 BCMA 更常发生。因此，抗 GPRC5D 免疫疗法必须在短时间内重创尽可能多的骨髓瘤细胞。在这里，我们利用MM的临床前模型对forimtamig进行了表征，它是一种新型的GPRC5D靶向TCB，具有2+1形式。与传统的 1+1 TCB 形式相比，forimtamig 与 GPRC5D N 端的二价结合具有更高的亲和力，这与形成更稳定的免疫突触以及更高的肿瘤细胞杀伤力和 T 细胞活化能力相关。通过使用正位小鼠 MM 模型，forimtamig 将 T 效应细胞招募到骨髓中，并诱导快速杀伤肿瘤，即使在采用阶梯剂量以减少细胞因子释放之后也是如此。forimtamig与标准治疗（SoC）药物（包括抗CD38抗体、免疫调节药物和蛋白酶体抑制剂）联用可提高反应的深度和持续时间。forimtamig与新型治疗药物（包括BCMA-TCB和脑龙E3连接酶调节药物（CELMoDs））的联合治疗效果显著，可防止GPRC5D阴性的肿瘤复发。目前，Forimtamig正在复发性和难治性骨髓瘤（RRMM）患者的单药治疗和联合治疗的1期临床试验中接受评估。NCT04557150。
{"title":"Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma.","authors":"Jan Eckmann, Tanja Fauti, Marlene Biehl, Aintzane Zabaleta, Laura Blanco, Iva Lelios, Stefan Gottwald, Richard Rae, Stefanie Lechner, Christa Bayer, Quincy Dekempe, Franz Osl, Nadege Carrié, Sahar Kassem, Stefan Lorenz, Tony Christopeit, Alejandro Carpy, Alexander Bujotzek, Ann-Marie Bröske, Iryna Dekhtiarenko, Jan Attig, Leo Kunz, Floriana Cremasco, Roberto Adelfio, Georg Fertig, Stefan Dengl, Christian Gassner, Felix Bormann, Claudia Kirstenpfad, Thomas Kraft, Sarah Diggelmann, Melanie Knobloch, Carina Hage, Romi Feddersen, Gordon Heidkamp, Thomas Pöschinger, Maud Mayoux, Luise Bernasconi, Felipe Prosper, Charles Dumontet, Ludovic Martinet, Stéphane Leclair, Wei Xu, Bruno Paiva, Christian Klein, Pablo Umaña","doi":"10.1182/blood.2024025987","DOIUrl":"10.1182/blood.2024025987","url":null,"abstract":"<p><strong>Abstract: </strong>Despite several approved therapies, multiple myeloma (MM) remains an incurable disease with high unmet medical need. \"Off-the-shelf\" T-cell bispecific antibodies (TCBs) targeting B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) have demonstrated high objective response rates in heavily pretreated patients with MM; however, primary resistance, short duration of response, and relapse driven by antigen shift frequently occur. Although GPRC5D represents the most selective target in MM, recent findings indicate antigen loss occurs more frequently than with BCMA. Thus, anti-GPRC5D immunotherapies must hit hard during a short period of time. Here, we characterize forimtamig, a novel GPRC5D-targeting TCB with 2+1 format. Bivalent binding of forimtamig to GPRC5D confers higher affinity than classical 1+1 TCB formats correlating with formation of more stable immunological synapses and higher potency in tumor cell killing and T-cell activation. Using an orthotopic mouse model of MM, forimtamig recruited T effector cells to the bone marrow and induced rapid tumor killing even after the introduction of step-up dosing to mitigate cytokine release. Combination of forimtamig with standard-of-care agents including anti-CD38 antibodies, immunomodulatory drugs, and proteasome inhibitors improved depth and duration of response. The combination of forimtamig with novel therapeutic agents including BCMA TCB and cereblon E3 ligase modulatory drugs was potent and prevented occurrence of GPRC5D -negative tumor relapse. Forimtamig is currently being evaluated in phase 1 clinical trials in patients with relapsed and refractory MM for monotherapy and in combination treatments. This trial was registered at www.ClinicalTrials.gov as #NCT04557150.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"202-219"},"PeriodicalIF":21.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-09DOI: 10.1182/blood.2024025707
Adrien Cottu, Stéphanie Guillet, Jean-François Viallard, Etienne Rivière, Stéphane Cheze, Delphine Gobert, Antoine Neel, Julie Graveleau, Jean-Pierre Marolleau, François Lefrere, Guillaume Moulis, Jean-Christophe Lega, Aline Moignet-Autrel, Ailsa Robbins, Etienne Crickx, Emmanuelle Boutin, Nicolas Noel, Marion Malphettes, Lionel Galicier, Sylvain Audia, Bernard Bonnotte, Olivier Lambotte, Olivier Fain, Mathieu Gerfaud-Valentin, Louis Terriou, Nihal Martis, Anne-Sophie Morin, Antoinette Perlat, Thomas Le Gallou, Frédérique Roy-Peaud, Matthieu Puyade, Thibault Comont, Nicolas Limal, Laetitia Languille, Marc Michel, Bertrand Godeau, Matthieu Mahevas
Abstract: In an open prospective, multicenter study enrolling 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation.
{"title":"Long-term follow-up of the STOPAGO study.","authors":"Adrien Cottu, Stéphanie Guillet, Jean-François Viallard, Etienne Rivière, Stéphane Cheze, Delphine Gobert, Antoine Neel, Julie Graveleau, Jean-Pierre Marolleau, François Lefrere, Guillaume Moulis, Jean-Christophe Lega, Aline Moignet-Autrel, Ailsa Robbins, Etienne Crickx, Emmanuelle Boutin, Nicolas Noel, Marion Malphettes, Lionel Galicier, Sylvain Audia, Bernard Bonnotte, Olivier Lambotte, Olivier Fain, Mathieu Gerfaud-Valentin, Louis Terriou, Nihal Martis, Anne-Sophie Morin, Antoinette Perlat, Thomas Le Gallou, Frédérique Roy-Peaud, Matthieu Puyade, Thibault Comont, Nicolas Limal, Laetitia Languille, Marc Michel, Bertrand Godeau, Matthieu Mahevas","doi":"10.1182/blood.2024025707","DOIUrl":"10.1182/blood.2024025707","url":null,"abstract":"<p><strong>Abstract: </strong>In an open prospective, multicenter study enrolling 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"244-247"},"PeriodicalIF":21.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-09DOI: 10.1182/blood.2024027362
Paola Neri
{"title":"Doubling down on GPRC5D in multiple myeloma.","authors":"Paola Neri","doi":"10.1182/blood.2024027362","DOIUrl":"https://doi.org/10.1182/blood.2024027362","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 2","pages":"146-148"},"PeriodicalIF":21.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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