{"title":"CAR-T cell therapy in Multiple Myeloma: current status and future challenges","authors":"Dawn Swan, Deepu Madduri, Jay Hocking","doi":"10.1038/s41408-024-01191-8","DOIUrl":"https://doi.org/10.1038/s41408-024-01191-8","url":null,"abstract":"<p>The treatment of multiple myeloma has changed dramatically in recent years, with huge strides forward made in the field. Chimeric antigen receptor T-cell therapy targeting the B cell maturation antigen (BCMA) is now widely approved in relapsed refractory patients and is moving into earlier treatment lines. In this review, we discuss the evidence underpinning current regulatory approvals and consider mechanisms through which CAR-T cell efficacy could be improved. These include tackling BCMA-loss, harnessing the immunosuppressive tumour microenvironment, manufacturing concerns including the potential role of other cellular sources, safety issues such as cytokine release syndrome and neurotoxicity, and optimal patient selection.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"27 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713093","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}
Jie Wang, Chun En Yau, Chen Ee Low, Mohamed Haniffa Bin Hasan Mohamed, Chee Leong Cheng, Jadee L. Neff, Jing Quan Lim, Soon Thye Lim, Jason Yongsheng Chan, Choon Kiat Ong, Valerie Shiwen Yang
{"title":"Indolent nodal T follicular helper cell lymphomas—A case series","authors":"Jie Wang, Chun En Yau, Chen Ee Low, Mohamed Haniffa Bin Hasan Mohamed, Chee Leong Cheng, Jadee L. Neff, Jing Quan Lim, Soon Thye Lim, Jason Yongsheng Chan, Choon Kiat Ong, Valerie Shiwen Yang","doi":"10.1038/s41408-024-01163-y","DOIUrl":"https://doi.org/10.1038/s41408-024-01163-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713081","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}
Elias J. Jabbour, Hagop M. Kantarjian, Nicola Goekbuget, Bijal D. Shah, Sabina Chiaretti, Jae H. Park, Anita W. Rijneveld, Lia Gore, Shaun Fleming, Aaron C. Logan, Josep M. Ribera, Tobias F. Menne, Khalid Mezzi, Faraz Zaman, Kelly Velasco, Nicolas Boissel
{"title":"Frontline Ph-negative B-cell precursor acute lymphoblastic leukemia treatment and the emerging role of blinatumomab","authors":"Elias J. Jabbour, Hagop M. Kantarjian, Nicola Goekbuget, Bijal D. Shah, Sabina Chiaretti, Jae H. Park, Anita W. Rijneveld, Lia Gore, Shaun Fleming, Aaron C. Logan, Josep M. Ribera, Tobias F. Menne, Khalid Mezzi, Faraz Zaman, Kelly Velasco, Nicolas Boissel","doi":"10.1038/s41408-024-01179-4","DOIUrl":"https://doi.org/10.1038/s41408-024-01179-4","url":null,"abstract":"<p>This narrative review seeks to summarize chemotherapeutic regimens commonly used for patients with newly diagnosed Philadelphia (Ph) chromosome–negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in the frontline setting and to describe the latest clinical research using the bispecific T-cell–engaging immunotherapy blinatumomab in the first-line treatment setting. Current standard-of-care chemotherapeutic backbones for newly diagnosed Ph-negative BCP-ALL are based on the same overarching treatment principle: to reduce disease burden to undetectable levels and maintain lasting remission. The adult treatment landscape has progressively evolved following the adoption of pediatric-inspired regimens. However, these intense regimens are not tolerated by all, and high-risk patients still have inferior outcomes. Therefore, designing more effective and less toxic strategies remains key to further improving efficacy and safety outcomes. Overall, the treatment landscape is evolving in the frontline, and integration of blinatumomab into different standard frontline regimens may improve overall outcomes with a favorable safety profile.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"38 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670896","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}
Moazzam Shahzad, Muhammad Kashif Amin, Naval G. Daver, Mithun Vinod Shah, Devendra Hiwase, Daniel A. Arber, Mohamed A. Kharfan-Dabaja, Talha Badar
{"title":"What have we learned about TP53-mutated acute myeloid leukemia?","authors":"Moazzam Shahzad, Muhammad Kashif Amin, Naval G. Daver, Mithun Vinod Shah, Devendra Hiwase, Daniel A. Arber, Mohamed A. Kharfan-Dabaja, Talha Badar","doi":"10.1038/s41408-024-01186-5","DOIUrl":"https://doi.org/10.1038/s41408-024-01186-5","url":null,"abstract":"<p><i>TP53</i> is a tumor suppressor gene frequently mutated in human cancers and is generally associated with poor outcomes. <i>TP53</i> mutations are found in approximately 5% to 10% of patients with de novo acute myeloid leukemia (AML), more frequently observed in elderly patients and those with therapy-related AML. Despite recent advances in molecular profiling and the emergence of targeted therapies, <i>TP53</i>-mutated AML remains a challenge to treat. Current treatment strategies, including conventional chemotherapy, hypomethylating agents, and venetoclax-based therapies, have shown limited efficacy in <i>TP53</i>-mutated AML, with low response rates and poor overall survival. Allogeneic hematopoietic stem cell transplantation is a potentially curative option; however, its efficacy in <i>TP53</i>-mutated AML depends on comorbid conditions and disease status at transplantation. Novel therapeutic modalities, including immune-based therapies, did show promise in early-phase studies but did not translate into effective therapies in randomized controlled trials. This review provides a comprehensive overview of <i>TP53</i> mutations in AML, outcomes based on allelic burden, clinical implications, and therapeutic challenges.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"18 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670897","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}
Jinha Hwang, Ha Nui Kim, Jung Ah Kwon, Soo-Young Yoon, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul Won Choi, Jung Yoon
{"title":"Impact of TP53 mutation on genetic and cellular hierarchy profile in complex karyotype AML/MDS with increased blasts","authors":"Jinha Hwang, Ha Nui Kim, Jung Ah Kwon, Soo-Young Yoon, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul Won Choi, Jung Yoon","doi":"10.1038/s41408-024-01188-3","DOIUrl":"https://doi.org/10.1038/s41408-024-01188-3","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"11 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637179","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}
Sikander Ailawadhi, Hans C. Lee, James Omel, Kathleen Toomey, James W. Hardin, Cristina J. Gasparetto, Sundar Jagannath, Robert M. Rifkin, Brian G. M. Durie, Mohit Narang, Howard R. Terebelo, Prashant Joshi, Ying-Ming Jou, Jorge Mouro, Edward Yu, Rafat Abonour
{"title":"Impact of lenalidomide-bortezomib-dexamethasone induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect® MM Registry","authors":"Sikander Ailawadhi, Hans C. Lee, James Omel, Kathleen Toomey, James W. Hardin, Cristina J. Gasparetto, Sundar Jagannath, Robert M. Rifkin, Brian G. M. Durie, Mohit Narang, Howard R. Terebelo, Prashant Joshi, Ying-Ming Jou, Jorge Mouro, Edward Yu, Rafat Abonour","doi":"10.1038/s41408-024-01177-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01177-6","url":null,"abstract":"<p>Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"10 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598040","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}
Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa
{"title":"Genetically determined telomere length in monoclonal gammopathy of undetermined significance, multiple myeloma risk and outcome.","authors":"Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa","doi":"10.1038/s41408-024-01181-w","DOIUrl":"10.1038/s41408-024-01181-w","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":"200"},"PeriodicalIF":12.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rossana Di Staso, Beatrice Casadei, Frederick L. Locke, Michael Jain, Timothy J. Voorhees, Adam S. Kittai, Mariana Bastos-Oreiro, Antonio Gutiérrez, Alejandro Martin Garcia-Sancho, Maria Jose Terol, Monica Mead, Michael J. Maranzano, Gloria Iacoboni, Pere Barba, Mi Kwon, Rebeca Bailen, Juan Luis Reguera-Ortega, Agrima Mian, Brian Hill, Emmanuel Bachy, Franck Morschhauser, Roch Houot, Catherine Thieblemont, Steven Le Gouill, Riccardo Masetti, Davide Gori, Alessandro Broccoli, Pier Luigi Zinzani, Lisa Argnani
{"title":"Is CAR T a drug or a therapeutic pathway? Intention to treat versus per protocol analysis of real world studies of CAR-T cell therapy in relapsed refractory diffuse large B cell lymphoma","authors":"Rossana Di Staso, Beatrice Casadei, Frederick L. Locke, Michael Jain, Timothy J. Voorhees, Adam S. Kittai, Mariana Bastos-Oreiro, Antonio Gutiérrez, Alejandro Martin Garcia-Sancho, Maria Jose Terol, Monica Mead, Michael J. Maranzano, Gloria Iacoboni, Pere Barba, Mi Kwon, Rebeca Bailen, Juan Luis Reguera-Ortega, Agrima Mian, Brian Hill, Emmanuel Bachy, Franck Morschhauser, Roch Houot, Catherine Thieblemont, Steven Le Gouill, Riccardo Masetti, Davide Gori, Alessandro Broccoli, Pier Luigi Zinzani, Lisa Argnani","doi":"10.1038/s41408-024-01183-8","DOIUrl":"https://doi.org/10.1038/s41408-024-01183-8","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"243 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594814","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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