Blood Cancer Discovery最新文献_第6页

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.bcd-4-6-iti

{"title":"Highlighted research articles","authors":"","doi":"10.1158/2643-3230.bcd-4-6-iti","DOIUrl":"https://doi.org/10.1158/2643-3230.bcd-4-6-iti","url":null,"abstract":"In This Issue| November 01 2023 Highlighted research articles Author & Article Information Online ISSN: 2643-3249 Print ISSN: 2643-3230 ©2023 American Association for Cancer Research2023American Association for Cancer Research Blood Cancer Discov (2023) 4 (6): 419. https://doi.org/10.1158/2643-3230.BCD-4-6-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 1 2023 Citation Highlighted research articles. Blood Cancer Discov 1 November 2023; 4 (6): 419. https://doi.org/10.1158/2643-3230.BCD-4-6-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Anti-BCMA bispecific T-cell engager antibodies (BiTE) have demonstrated impressive efficacy in heavily relapsed multiple myeloma patients; however, infections remain a serious concern with these therapies. In this article, Lancman et al. demonstrate that profound and prolonged hypogammaglobulinemia is universal in patients responding to therapy and is a significant driver of infections. Intravenous immunoglobulin (IVIg) replacement mitigates the risk of serious infections ten-fold. The findings support IVIg as a primary prophylaxis throughout the duration of therapy and raise questions about the optimal schedule and duration of BiTE treatment. See article, p. 440. The combination of azacytidine with venetoclax has become the standard first-line treatment for patients with acute myeloid leukemia (AML) unable to tolerate chemotherapy. However, there is still unmet need for not only identifying poor-responding patients but also identifying effective therapeutic strategies for them. In this precision medicine proof-of-concept study, Eide, Kurtz et al. implement ex vivo screening of... You do not currently have access to this content.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"292 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135272192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Year of Advances in Precision Therapy for Blood Cancers. 血癌精准治疗进展一年。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0193

引用次数: 0

Potent Personalized Venetoclax Partners for Acute Myeloid Leukemia Identified by Ex Vivo Drug Screening. 通过体外药物筛选鉴定急性髓细胞白血病的强效个性化Venetoclax伴侣。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0180

Pamela S Becker

引用次数: 0

Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells. 白血病祖细胞HLA抗原介导的急性粒细胞白血病免疫监测。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0020

Annika Nelde, Heiko Schuster, Jonas S Heitmann, Jens Bauer, Yacine Maringer, Melissa Zwick, Jens-Peter Volkmer, James Y Chen, Anna M Paczulla Stanger, Ariane Lehmann, Bismark Appiah, Melanie Märklin, Elke Rücker-Braun, Helmut R Salih, Malte Roerden, Sarah M Schroeder, Max-Felix Häring, Andreas Schlosser, Johannes Schetelig, Marc Schmitz, Melanie Boerries, Natalie Köhler, Claudia Lengerke, Ravindra Majeti, Irving L Weissman, Hans-Georg Rammensee, Juliane S Walz

{"title":"Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.","authors":"Annika Nelde, Heiko Schuster, Jonas S Heitmann, Jens Bauer, Yacine Maringer, Melissa Zwick, Jens-Peter Volkmer, James Y Chen, Anna M Paczulla Stanger, Ariane Lehmann, Bismark Appiah, Melanie Märklin, Elke Rücker-Braun, Helmut R Salih, Malte Roerden, Sarah M Schroeder, Max-Felix Häring, Andreas Schlosser, Johannes Schetelig, Marc Schmitz, Melanie Boerries, Natalie Köhler, Claudia Lengerke, Ravindra Majeti, Irving L Weissman, Hans-Georg Rammensee, Juliane S Walz","doi":"10.1158/2643-3230.BCD-23-0020","DOIUrl":"10.1158/2643-3230.BCD-23-0020","url":null,"abstract":"Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid leukemia (AML) relapse. LSC-targeting therapies may thus improve outcome of patients with AML. Here we demonstrate that LSCs present HLA-restricted antigens that induce T-cell responses allowing for immune surveillance of AML. Using a mass spectrometry-based immunopeptidomics approach, we characterized the antigenic landscape of patient LSCs and identified AML- and AML/LSC-associated HLA-presented antigens absent from normal tissues comprising nonmutated peptides, cryptic neoepitopes, and neoepitopes of common AML driver mutations of NPM1 and IDH2. Functional relevance of shared AML/LSC antigens is illustrated by presence of their cognizant memory T cells in patients. Antigen-specific T-cell recognition and HLA class II immunopeptidome diversity correlated with clinical outcome. Together, these antigens shared among AML and LSCs represent prime targets for T cell-based therapies with potential of eliminating residual LSCs in patients with AML.Significance: The elimination of therapy-resistant leukemia stem and progenitor cells (LSC) remains a major challenge in the treatment of AML. This study identifies and functionally validates LSC-associated HLA class I and HLA class II-presented antigens, paving the way to the development of LSC-directed T cell-based immunotherapeutic approaches for patients with AML. See related commentary by Ritz, p. 430 . This article is featured in Selected Articles from This Issue, p. 419.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"468-489"},"PeriodicalIF":11.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41239314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies. 抗BCMA双特异性抗体治疗的多发性骨髓瘤患者使用IVIg可将严重感染减少10倍。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0049

Guido Lancman, Kian Parsa, Krzysztof Kotlarz, Lisa Avery, Alaina Lurie, Alex Lieberman-Cribbin, Hearn Jay Cho, Samir S Parekh, Shambavi Richard, Joshua Richter, Cesar Rodriguez, Adriana Rossi, Larysa J Sanchez, Santiago Thibaud, Sundar Jagannath, Ajai Chari

{"title":"IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies.","authors":"Guido Lancman, Kian Parsa, Krzysztof Kotlarz, Lisa Avery, Alaina Lurie, Alex Lieberman-Cribbin, Hearn Jay Cho, Samir S Parekh, Shambavi Richard, Joshua Richter, Cesar Rodriguez, Adriana Rossi, Larysa J Sanchez, Santiago Thibaud, Sundar Jagannath, Ajai Chari","doi":"10.1158/2643-3230.BCD-23-0049","DOIUrl":"10.1158/2643-3230.BCD-23-0049","url":null,"abstract":"BCMA-targeted bispecific antibodies (BiAb) are efficacious in relapsed/refractory multiple myeloma; however, serious infections have emerged as important toxicities. In this retrospective study, we characterized all infections and their risk factors, and evaluated the impact of infection prophylaxis in patients treated with BCMA-targeted BiAbs. Among 37 patients, 15 (41%) experienced a grade 3-5 infection, with two infection-related deaths during deep remissions. Most (84%) infections occurred during disease remissions. The cumulative probability of grade 3-5 infection increased over time with no plateau. Among responders (n = 26), profound hypogammaglobulinemia occurred in 100% and continued throughout the entire duration of treatment. During periods when patients were receiving intravenous immunoglobulin (IVIg), the rate of grade 3-5 infections was 90% lower than during observation (incidence rate ratio, 0.10; 95% confidence interval, 0.01-0.80; P = 0.0307). No other risk factors for infection were identified. This study demonstrates that profound hypogammaglobulinemia is universal with BCMA-targeted BiAbs, with intravenous immunoglobulin potentially abrogating most of the infection risk.Significance: To the best of our knowledge, this is the first study to comprehensively analyze risk factors and mitigation strategies to prevent infections in myeloma patients receiving anti-BCMA bispecific antibodies. Profound and prolonged hypogammaglobulinemia was universal among responders, while immunoglobulin replacement was associated with 90% lower rates of grade 3-5 infections. See related commentary by Garfall and Stadtmauer, p. 427 . This article is featured in Selected Articles from This Issue, p. 419.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"440-451"},"PeriodicalIF":11.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41131345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Correlates of Venetoclax-Based Combination Sensitivities to Augment Acute Myeloid Leukemia Therapy. 以Venetoclax为基础的联合用药对增强急性髓细胞白血病治疗的临床相关性。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0014

Christopher A Eide, Stephen E Kurtz, Andy Kaempf, Nicola Long, Sunil Kumar Joshi, Tamilla Nechiporuk, Ariane Huang, Charles A Dibb, Akosha Taylor, Daniel Bottomly, Shannon K McWeeney, Jessica Minnier, Curtis A Lachowiez, Jennifer N Saultz, Ronan T Swords, Anupriya Agarwal, Bill H Chang, Brian J Druker, Jeffrey W Tyner

{"title":"Clinical Correlates of Venetoclax-Based Combination Sensitivities to Augment Acute Myeloid Leukemia Therapy.","authors":"Christopher A Eide, Stephen E Kurtz, Andy Kaempf, Nicola Long, Sunil Kumar Joshi, Tamilla Nechiporuk, Ariane Huang, Charles A Dibb, Akosha Taylor, Daniel Bottomly, Shannon K McWeeney, Jessica Minnier, Curtis A Lachowiez, Jennifer N Saultz, Ronan T Swords, Anupriya Agarwal, Bill H Chang, Brian J Druker, Jeffrey W Tyner","doi":"10.1158/2643-3230.BCD-23-0014","DOIUrl":"10.1158/2643-3230.BCD-23-0014","url":null,"abstract":"The BCL2 inhibitor venetoclax combined with the hypomethylating agent azacytidine shows significant clinical benefit in a subset of patients with acute myeloid leukemia (AML); however, resistance limits response and durability. We prospectively profiled the ex vivo activity of 25 venetoclax-inclusive combinations on primary AML patient samples to identify those with improved potency and synergy compared with venetoclax + azacytidine (Ven + azacytidine). Combination sensitivities correlated with tumor cell state to discern three patterns: primitive selectivity resembling Ven + azacytidine, monocytic selectivity, and broad efficacy independent of cell state. Incorporation of immunophenotype, mutation, and cytogenetic features further stratified combination sensitivity for distinct patient subtypes. We dissect the biology underlying the broad, cell state-independent efficacy for the combination of venetoclax plus the JAK1/2 inhibitor ruxolitinib. Together, these findings support opportunities for expanding the impact of venetoclax-based drug combinations in AML by leveraging clinical and molecular biomarkers associated with ex vivo responses.Significance: By mapping drug sensitivity data to clinical features and tumor cell state, we identify novel venetoclax combinations targeting patient subtypes who lack sensitivity to Ven + azacytidine. This provides a framework for a taxonomy of AML informed by readily available sets of clinical and genetic features obtained as part of standard care. See related commentary by Becker, p. 437 . This article is featured in Selected Articles from This Issue, p. 419.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"452-467"},"PeriodicalIF":11.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunologic Targets in AML. AML的免疫靶点。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0161

Jerome Ritz

引用次数: 0

AACR Cancer Centers Alliance: Fostering Collaboration and Innovation to Advance Lifesaving Scientific Discoveries for Patients. 癌症中心联盟：促进合作和创新，促进患者的救生科学发现。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-11-01 DOI: 10.1158/2643-3230.BCD-23-0187

Carlos L Arteaga, John L Cleveland, Margaret Foti, Ruben A Mesa, Louis M Weiner, Cheryl L Willman, David A Tuveson

引用次数: 0

Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel. Idecbtagene Vicleucel后血清学和可测量残留疾病评估的时间依赖性预后价值。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-09-01 DOI: 10.1158/2643-3230.BCD-23-0044

Bruno Paiva, Irene Manrique, Julie Rytlewski, Timothy Campbell, Christian C Kazanecki, Nathan Martin, Larry D Anderson, Jesús G Berdeja, Sagar Lonial, Noopur S Raje, Yi Lin, Philippe Moreau, Jesús F San-Miguel, Nikhil C Munshi, Shari M Kaiser

{"title":"Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel.","authors":"Bruno Paiva, Irene Manrique, Julie Rytlewski, Timothy Campbell, Christian C Kazanecki, Nathan Martin, Larry D Anderson, Jesús G Berdeja, Sagar Lonial, Noopur S Raje, Yi Lin, Philippe Moreau, Jesús F San-Miguel, Nikhil C Munshi, Shari M Kaiser","doi":"10.1158/2643-3230.BCD-23-0044","DOIUrl":"10.1158/2643-3230.BCD-23-0044","url":null,"abstract":"The role of measurable residual disease (MRD) in multiple myeloma patients treated with chimeric antigen receptor (CAR) T cells is uncertain. We analyzed MRD kinetics during the first year after idecabtagene vicleucel (ide-cel) infusion in 125 relapsed/refractory multiple myeloma patients enrolled in KarMMa. At month 1 after ide-cel, there were no differences in progression-free survival (PFS) between patients in less than complete response (CR) versus those in CR; only MRD status was predictive of significantly different PFS at this landmark. In patients with undetectable MRD at 3 months and beyond, PFS was longer in those achieving CR versus <CR. Persistent MRD in the 10-6 logarithmic range and reappearance of normal plasma cells in MRD-negative patients were associated with inferior PFS. This study unveils different prognostic implications of serological and MRD response dynamics after ide-cel and suggests the potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR T-cell functionality.Significance: This is one of the first studies evaluating the impact of CR and MRD dynamics after CAR T therapy in relapsed/refractory multiple myeloma. These data help interpret the prognostic significance of serological and MRD responses at early and late time points after CAR T-cell infusion. See related commentary by Landgren and Kazandjian, p. 346 . This article is featured in Selected Articles from This Issue, p. 337.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"365-373"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches. 用于治疗骨髓增生性肿瘤的下一代JAK2抑制剂：基于结构的药物发现方法的经验教训。

IF 11.2

Blood Cancer Discovery Pub Date : 2023-09-01 DOI: 10.1158/2643-3230.BCD-22-0189

Pramod C Nair, Jacob Piehler, Denis Tvorogov, David M Ross, Angel F Lopez, Jason Gotlib, Daniel Thomas

{"title":"Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches.","authors":"Pramod C Nair, Jacob Piehler, Denis Tvorogov, David M Ross, Angel F Lopez, Jason Gotlib, Daniel Thomas","doi":"10.1158/2643-3230.BCD-22-0189","DOIUrl":"10.1158/2643-3230.BCD-22-0189","url":null,"abstract":"Selective inhibitors of Janus kinase (JAK) 2 have been in demand since the discovery of the JAK2 V617F mutation present in patients with myeloproliferative neoplasms (MPN); however, the structural basis of V617F oncogenicity has only recently been elucidated. New structural studies reveal a role for other JAK2 domains, beyond the kinase domain, that contribute to pathogenic signaling. Here we evaluate the structure-based approaches that led to recently-approved type I JAK2 inhibitors (fedratinib and pacritinib), as well as type II (BBT594 and CHZ868) and pseudokinase inhibitors under development (JNJ7706621). With full-length JAK homodimeric structures now available, superior selective and mutation-specific JAK2 inhibitors are foreseeable.Significance: The JAK inhibitors currently used for the treatment of MPNs are effective for symptom management but not for disease eradication, primarily because they are not strongly selective for the mutant clone. The rise of computational and structure-based drug discovery approaches together with the knowledge of full-length JAK dimer complexes provides a unique opportunity to develop better targeted therapies for a range of conditions driven by pathologic JAK2 signaling.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"4 5","pages":"352-364"},"PeriodicalIF":11.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0