Ricardo D. Parrondo, Saurav Das, Hanna Sledge, Leif Bergsagel, Rafael Fonseca, Nelson Leung, Prashant Kapoor, Morie Gertz, Francis Buadi, Angela Dispenzieri, Jamie Elliott, Andre Fernandez, Caitlin Flott, Asher A. Chanan-Khan, Vivek Roy, Sikander Ailawadhi
{"title":"Real world outcomes with elotuzumab-based therapies for patients with relapsed refractory multiple myeloma: a Mayo Clinic experience","authors":"Ricardo D. Parrondo, Saurav Das, Hanna Sledge, Leif Bergsagel, Rafael Fonseca, Nelson Leung, Prashant Kapoor, Morie Gertz, Francis Buadi, Angela Dispenzieri, Jamie Elliott, Andre Fernandez, Caitlin Flott, Asher A. Chanan-Khan, Vivek Roy, Sikander Ailawadhi","doi":"10.1038/s41408-025-01310-z","DOIUrl":"https://doi.org/10.1038/s41408-025-01310-z","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"20 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122617","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}
Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D DiNardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M McGeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla
{"title":"Correction: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.","authors":"Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D DiNardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M McGeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla","doi":"10.1038/s41408-025-01306-9","DOIUrl":"10.1038/s41408-025-01306-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"99"},"PeriodicalIF":12.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118690","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}
{"title":"Genomic and transcriptomic determinants of clinical outcomes in patients with AML and DNMT3A mutations","authors":"Sao-Chih Ni, Chi-Yuan Yao, Xavier Cheng-Hong Tsai, Min-Yen Lo, Chien-Yuan Chen, Wan-Hsuan Lee, Chien-Chin Lin, Yuan-Yeh Kuo, Yen-Ling Peng, Mei-Hsuan Tseng, Yu-Sin Wu, Ming-Chih Liu, Liang-In Lin, Ming-Kai Chuang, Bor-Sheng Ko, Ming Yao, Jih-Luh Tang, Feng-Ming Tien, Wen-Chien Chou, Hsin-An Hou, Hwei-Fang Tien","doi":"10.1038/s41408-025-01287-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01287-9","url":null,"abstract":"<p>Acute myeloid leukemia (AML) and <i>DNMT3A</i> mutations (<i>DNMT3A</i><sup>mut</sup>) are considered to carry intermediate risk under the 2022 European LeukemiaNet (ELN-2022) classification in the absence of other co-mutations or cytogenetic abnormalities. However, this group is highly heterogeneous. In this study, the genomic and transcriptomic features influencing outcomes in <i>DNMT3A</i>-mutated AML were examined in a cohort of 884 patients with AML receiving standard chemotherapy. Stratification by <i>NPM1</i> and <i>FLT3</i>-ITD status revealed worse survival among patients with <i>NPM1</i> mutations and wild-type <i>FLT3</i>-ITD (<i>NPM1</i><sup>mut</sup>/<i>FLT3-</i>ITD<sup>wt</sup>) than patients in the ELN-2022 favorable risk group. The other three subgroups (<i>NPM1</i><sup>mut</sup>/<i>FLT3-</i>ITD<sup>mut</sup>, <i>NPM1</i><sup>wt</sup>/<i>FLT3-</i>ITD<sup>mut</sup>, and <i>NPM1</i><sup>wt</sup>/<i>FLT3-</i>ITD<sup>wt</sup>) exhibited worse prognoses than patients in the ELN-2022 intermediate risk group. Additionally, the presence of <i>TET2</i><sup>mut</sup> in patients with AML and <i>DNMT3A</i><sup>mut</sup>/<i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-ITD<sup>wt</sup> led to reclassification from favorable risk to intermediate risk in the ELN-2022. RNA-sequencing analysis revealed a distinct transcriptomic profile in patients with <i>TET2</i><sup>mut</sup>, highlighting the enrichment of leukemic stem cell signatures and dendritic cell migration, with <i>MMP14</i>, <i>CD200</i>, and <i>CT45A5</i> identified as key differentially expressed genes. In conclusion, co-mutation patterns strongly affected AML outcomes in patients with <i>DNMT3A</i><sup>mut</sup>. Patients with <i>TET2</i><sup>mut</sup> constituted a unique subgroup within the ELN-2022 favorable <i>DNMT3A</i><sup>mut</sup>/<i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-ITD<sup>wt</sup> group, characterized by distinct transcriptomic features and an unfavorable prognosis.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"131 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097234","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}
Sandra Huber, Stephan Hutter, Constance Baer, Manja Meggendorfer, Gregor Hoermann, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach
{"title":"Two ways to complex karyotype in MDS—the role of del(5q) and TP53","authors":"Sandra Huber, Stephan Hutter, Constance Baer, Manja Meggendorfer, Gregor Hoermann, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach","doi":"10.1038/s41408-025-01305-w","DOIUrl":"https://doi.org/10.1038/s41408-025-01305-w","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"73 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097235","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}
Carlos Jimenez-Vicente, Aina Cardus, Sandra Castaño-Diez, Guillermo Ramil, Sara Garcia-Avila, Lucia Gomez-Perez, Daniel Esteban, Iago Arribas, Antonella Lucia Sturla, Monica Lopez-Guerra, Alexandra Martinez-Roca, Albert Cortes-Bullich, Amanda Isabel Perez-Valencia, Ines Zugasti, Ines Monge, Esther Carcelero, Ferran Vall-Llovera, Susana Vives, Jorge Sierra, Josep Nomdedeu, Guadalupe Oñate, Ana Garrido, Marta Pratcorona, Helena Pomares, Montserrat Arnan, Francesca Guijarro, Marina Diaz-Beya, Jordi Esteve
{"title":"Prognostic value of measurable residual disease (MRD) for venetoclax in combination with hypomethylating agents in patients diagnosed with acute myeloid leukemia: validation of the ELN-2021 MRD recommendations","authors":"Carlos Jimenez-Vicente, Aina Cardus, Sandra Castaño-Diez, Guillermo Ramil, Sara Garcia-Avila, Lucia Gomez-Perez, Daniel Esteban, Iago Arribas, Antonella Lucia Sturla, Monica Lopez-Guerra, Alexandra Martinez-Roca, Albert Cortes-Bullich, Amanda Isabel Perez-Valencia, Ines Zugasti, Ines Monge, Esther Carcelero, Ferran Vall-Llovera, Susana Vives, Jorge Sierra, Josep Nomdedeu, Guadalupe Oñate, Ana Garrido, Marta Pratcorona, Helena Pomares, Montserrat Arnan, Francesca Guijarro, Marina Diaz-Beya, Jordi Esteve","doi":"10.1038/s41408-025-01298-6","DOIUrl":"https://doi.org/10.1038/s41408-025-01298-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"68 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979665","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}
Craig A. Portell, Opeyemi A. Jegede, Nina Wagner-Johnston, Grzegorz S. Nowakowski, Christopher Fletcher, Jonathon B. Cohen, Andrew M. Evens, Lori J. Rosenstein, Jeffrey W. Craig, Nishitha Reddy, Brad S. Kahl
{"title":"Phase II study of venetoclax added to bendamustine and obinutuzumab in patients with high-risk follicular lymphoma as front-line therapy: PrE0403","authors":"Craig A. Portell, Opeyemi A. Jegede, Nina Wagner-Johnston, Grzegorz S. Nowakowski, Christopher Fletcher, Jonathon B. Cohen, Andrew M. Evens, Lori J. Rosenstein, Jeffrey W. Craig, Nishitha Reddy, Brad S. Kahl","doi":"10.1038/s41408-025-01300-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01300-1","url":null,"abstract":"<p>Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate to 65% with an 85% power and 15% type I error rate. Immunohistochemistry (IHC) expression of 3 antiapoptotic proteins (BCL-xL, MCL-1, and BCL-2) was performed and correlated with clinical outcomes. All 56 subjects were eligible and treated. CR rate was 41/56 (73.2%) and ORR was 52/56 (92.5%) meeting the primary endpoint. 2-year estimated PFS was 87.5% (90% CI: 75.3,93.9%) and 2-year estimated OS was 94.6% (90% CI: 86.7, 97.9%). However, the incidence of treatment-related adverse events ≥ grade 3 was 83.9% and serious adverse events were seen in 57.1%. After induction, atypical infections, including Grade 5 events, occurred. Anti-apoptotic protein expression by IHC was not correlated with clinical outcomes. Thus, while meeting the primary efficacy end point, VEN-OB is considered overly toxic in high-risk FL.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"14 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940204","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}
Oren Pasvolsky, Danai Dima, Lei Feng, Wenli Dong, Tiffany Richards, James A. Davis, Aimaz Afrough, Mariola Vazquez-Martinez, Aishwarya Sannareddy, Utkarsh Goel, Rahul Banerjee, Jack Khouri, Frances Cervoni, Mahmoud R. Gaballa, Alex Lieberman-Cribbin, Masooma Shifa Rana, Kelley Julian, Christopher J. Ferreri, Leyla Shune, Shaun DeJarnette, Evguenia Bhurtel, Sandra Susanibar Adaniya, Andrew Portuguese, Hitomi Hosoya, Lekha Mikkilineni, Gurbakhash Kaur, Adriana Rossi, Megan M. Herr, Daniel Schrum, Chenyu Lin, Shahzad Raza, Yi Lin, Shonali Midha, Nadeem Omar, Shebli Atarsh, Joseph McGuirk, Douglas Sborov, Peter Voorhees, Faiz Anwer, Melissa Alsina, Ciara Freeman, Alfred L. Garfall, Beatrice M. Razzo, Surbhi Sidana, Andrew J. Cowan, Larry D. Anderson Jr, Doris K. Hansen, Shambavi Richard, Krina K. Patel, Hans C. Lee, Ariel Grajales-Cruz
{"title":"Outcomes of elderly patients with relapsed refractory multiple myeloma (RRMM) treated with teclistamab: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium","authors":"Oren Pasvolsky, Danai Dima, Lei Feng, Wenli Dong, Tiffany Richards, James A. Davis, Aimaz Afrough, Mariola Vazquez-Martinez, Aishwarya Sannareddy, Utkarsh Goel, Rahul Banerjee, Jack Khouri, Frances Cervoni, Mahmoud R. Gaballa, Alex Lieberman-Cribbin, Masooma Shifa Rana, Kelley Julian, Christopher J. Ferreri, Leyla Shune, Shaun DeJarnette, Evguenia Bhurtel, Sandra Susanibar Adaniya, Andrew Portuguese, Hitomi Hosoya, Lekha Mikkilineni, Gurbakhash Kaur, Adriana Rossi, Megan M. Herr, Daniel Schrum, Chenyu Lin, Shahzad Raza, Yi Lin, Shonali Midha, Nadeem Omar, Shebli Atarsh, Joseph McGuirk, Douglas Sborov, Peter Voorhees, Faiz Anwer, Melissa Alsina, Ciara Freeman, Alfred L. Garfall, Beatrice M. Razzo, Surbhi Sidana, Andrew J. Cowan, Larry D. Anderson Jr, Doris K. Hansen, Shambavi Richard, Krina K. Patel, Hans C. Lee, Ariel Grajales-Cruz","doi":"10.1038/s41408-025-01297-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01297-7","url":null,"abstract":"<p>Teclistamab, a BCMA-directed bispecific antibody, received regulatory approval for relapsed/refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. Despite the fact that myeloma is primarily a cancer of elderly adults, only 15% of MajesTEC-1 participants (<i>n</i> = 24) were ≥75 years old. In this multicenter retrospective study, we report real-world outcomes of a large cohort of older RRMM patients treated with teclistamab. Of 385 analyzed patients, 83 (22%) were in the older group (age ≥75) and 302 (78%) in the younger group (age <75). Compared to the younger group, the older group had less adverse baseline disease characteristics, including a lower incidence of high-risk cytogenetics (44.6% vs. 57.9%, <i>p</i> = 0.03) and extramedullary disease (22% vs. 40%, <i>p</i> = 0.02). There were no significant differences in rates of any-grade CRS (52% vs. 59%, <i>p</i> = 0.27), any-grade ICANS (19% vs. 13%, <i>p</i> = 0.12), and overall response rate (62% vs. 53%, <i>p</i> = 0.17) between the older and younger groups. In multivariable analysis, age was not significantly associated with survival outcomes. Our findings suggest that teclistamab is safe and efficacious in well-selected patients ≥75 years old, and advanced age alone should not preclude teclistamab administration.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"146 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930935","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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