Blood Cancer Discovery最新文献

{"title":"Models, Models, Everywhere: But Which One Should Guide Care?","authors":"Curtis A Lachowiez, Sanam Loghavi","doi":"10.1158/2643-3230.BCD-26-0055","DOIUrl":"10.1158/2643-3230.BCD-26-0055","url":null,"abstract":"<p><p>Drekolias and colleagues report a therapy-specific prognostic model integrating mutational and cytogenetic features to risk-stratify survival in patients with acute myeloid leukemia treated with venetoclax-based regimens, providing a clinically relevant framework amid a rapidly expanding landscape of competing models. See related article by Drekolias et al., p. 403.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"339-342"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582353","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}

{"title":"Clinical Scores to Predict Toxicities and Outcomes in Patients with Multiple Myeloma Undergoing Bispecific T-cell Engager Therapy.","authors":"Jan H Frenking, Christine Riedhammer, Thomas Hielscher, Christoph Schaefers, Lisa B Leypoldt, Marie Harzer, David Sedloev, Valentine Landrin, Niklas Kehl, Mirco J Friedrich, Xiang Zhou, Maximilian Steinhardt, Philipp Weis, Julia Mersi, Johannes Waldschmidt, Niels Weinhold, K Martin Kortüm, Carsten Müller-Tidow, Hermann Einsele, Sandra Sauer, Katja Weisel, Tim Richardson, Raphael Teipel, Leo Rasche, Marc S Raab","doi":"10.1158/2643-3230.BCD-25-0062","DOIUrl":"10.1158/2643-3230.BCD-25-0062","url":null,"abstract":"<p><p>The significant clinical benefit of bispecific T-cell engagers (TCE) for the treatment of relapsed/refractory multiple myeloma (RRMM) may be offset by serious toxicities and treatment failure. Risk scores such as the CAR-HEMATOTOX (HTX), Endothelial Activation and Stress Index (EASIX), and modified EASIX (m-EASIX) can identify patients at risk for complications before chimeric antigen receptor (CAR) T-cell therapy, but their utility prior to TCE therapy remains elusive. We analyzed associations with outcomes and toxicities in independent discovery (n = 123) and validation (n = 155) cohorts treated with TCEs. Patients with HTX ≥3 or m-EASIX > median (>0.86) had a significantly increased risk of prolonged hospitalization, antibiotic treatment, and fever during step-up dosing. We also observed associations with cytopenias requiring therapeutic intervention, higher severe infection and intervention densities, as well as inferior response rates and reduced progression-free and overall survival. Our findings highlight the potential of these clinical scores to improve risk stratification before TCE therapy.</p><p><strong>Significance: </strong>Scores such as HTX, EASIX, and m-EASIX have emerged as helpful tools to enable risk stratification before CAR T-cell therapy. In this study, we demonstrate their utility in patients with RRMM receiving TCEs. HTX ≥3 and m-EASIX > median (>0.86) proved to be risk markers for infections, therapeutic interventions, and poor outcomes. See related commentary by Banerjee and Dhodapkar, p. 345.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"479-495"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195633","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}

{"title":"Outstanding Questions to Understand and Target Splicing Factor-Mutant Blood Cancers.","authors":"Maxim I Maron, Omar Abdel-Wahab","doi":"10.1158/2643-3230.BCD-26-0047","DOIUrl":"10.1158/2643-3230.BCD-26-0047","url":null,"abstract":"<p><p>Mutations in genes encoding RNA splicing factors are common in patients with myeloid malignancies and chronic lymphocytic leukemia. In this commentary, we discuss key unanswered questions on the causal role of these mutations in blood cancers and precursor conditions as well as efforts to develop therapies targeting these high-frequency neomorphic mutations.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"348-352"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13229135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147783186","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}

{"title":"Debulking Chemotherapy Can Overcome Primary Resistance to Teclistamab in Relapsed/Refractory Multiple Myeloma.","authors":"Rintu Sharma, Andree-Anne Pelland, Katherine Lajkosz, Esther Masih-Khan, Harjot Singh Vohra, Sita Bhella, Christine I Chen, Vishal Kukreti, A Keith Stewart, Suzanne Trudel, Chloe Yang, Donna E Reece, Chris Venner, Guido Lancman","doi":"10.1158/2643-3230.BCD-25-0372","DOIUrl":"10.1158/2643-3230.BCD-25-0372","url":null,"abstract":"<p><p>Bispecific antibodies have revolutionized the treatment of multiple myeloma; however, primary treatment failure occurs in 30% to 40% of patients. In this study, we analyzed correlates of response to teclistamab and strategies to overcome primary resistance. Across two independent cohorts (n = 90), we developed the high risk of primary resistance (Hi-MM) variable, defined by extramedullary disease, plasma cell leukemia, bone marrow plasmacytosis ≥50%, or transfusion within 30 days, as a composite correlate of nonresponse. Patients without Hi-MM had overall response rates of 84% to 96% (vs. 20%-40% with Hi-MM) and significantly superior progression-free survival (P < 0.001) and overall survival (P < 0.001). Debulking chemotherapy was utilized in 19 patients; 79% then responded to teclistamab, including 100% who no longer had Hi-MM. All four patients who were primary refractory to a BCMA bispecific immediately prior to debulking then achieved deep responses to teclistamab. In conclusion, simple clinical parameters correlate with response to teclistamab, whereas debulking chemotherapy can overcome Hi-MM and successfully bridge patients to teclistamab or salvage nonresponders.</p><p><strong>Significance: </strong>A clinically assessable composite variable, Hi-MM, identifies patients who may benefit from debulking chemotherapy prior to teclistamab. By treating patients at a time of low disease burden or using debulking chemotherapy for those with a high risk of resistance, nearly all patients can benefit from the deep and durable remissions induced by teclistamab.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"394-402"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436265","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}

{"title":"Two Costimulations Are Better Than One: Role of Endogenous CD28 in 4-1BB CAR T Cells.","authors":"Mohamad Hamieh, Michel Sadelain","doi":"10.1158/2643-3230.BCD-25-0491","DOIUrl":"10.1158/2643-3230.BCD-25-0491","url":null,"abstract":"<p><p>Liberman and colleagues identify endogenous CD28 signaling as a regulator of 4-1BB chimeric antigen receptor (CAR) T-cell function by promoting metabolic fitness, proliferation, and sustained antitumor function. These findings highlight the cooperative integration of CD28 and 4-1BB signaling to harness CAR T-cell potency, persistence, and therapeutic efficacy. See related article by Lieberman et al., p. 441.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"343-344"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475377","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}

{"title":"Incorporating ALL Biology into Treatment Decisions: Next Steps toward Targeted Therapy in Adult ALL.","authors":"Caner Saygin, Matthew T Witkowski, Sinan Cetin, Ibrahim Aldoss, Marlise R Luskin","doi":"10.1158/2643-3230.BCD-25-0078","DOIUrl":"10.1158/2643-3230.BCD-25-0078","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) management is evolving from a generalized approach toward a precision medicine paradigm driven by molecular heterogeneity. This review highlights how genomic profiling identifies high-risk subtypes, including KMT2A-rearranged, IKZF1-plus BCR::ABL1-positive, BCR::ABL1-like, and TP53-mutant B-cell ALL, which necessitate tailored therapies. We explore novel strategies such as BH3 mimetics, menin inhibitors, pre-T-cell receptor signaling blockade, and targeted immunotherapy, which show promise in relapsed/refractory and high-risk groups. We also address emerging challenges, including therapy-induced phenotypic escape mechanisms such as lineage switch and antigen loss. The future of ALL therapy lies in integrating these biology-driven approaches to improve outcomes across all age groups.</p><p><strong>Significance: </strong>This review provides a roadmap for the targeted therapy era in ALL, defining high-risk molecular subtypes and their targeted vulnerabilities. It synthesizes advances in BH3 mimetics, menin inhibition, and immunotherapy, while addressing the critical challenges of treatment resistance and phenotypic escape that define the next frontier of research.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"369-379"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575610","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}

{"title":"Incorporation of Genomic Determinants Improves Diagnostic Accuracy of Oligomonocytic Chronic Myelomonocytic Leukemia.","authors":"Guillermo Montalban-Bravo, Chong Wu, Juan Jose Rodriguez-Sevilla, Yue Wei, Kelly S Chien, Ian Bouligny, Rashmi Kanagal-Shamanna, Ziyi Li, Anuya Natu, Mark Gurney, Alexandre Bazinet, Danielle Hammond, Alex Bataller, Gautam Borthakur, Nicholas J Short, Courtney D DiNardo, Tapan M Kadia, Farhad Ravandi, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Ghayas C Issa, Sa A Wang, Keyur P Patel, Guilin Tang, L Jeffrey Medeiros, Terra L Lasho, Christy M Finke, Aref Al-Kali, Clifford M Csizmar, Hassan Alkhateeb, Naseema Gangat, Abhishek A Mangaonkar, David Roman-Bravo, Leonor Arenillas, Ayalew Tefferi, Hagop M Kantarjian, Guillermo Garcia-Manero, Xavier Calvo, Mrinal M Patnaik, Sanam Loghavi","doi":"10.1158/2643-3230.BCD-25-0264","DOIUrl":"10.1158/2643-3230.BCD-25-0264","url":null,"abstract":"<p><p>Recent updates to monocyte count thresholds recognize oligomonocytic chronic myelomonocytic leukemia (OM-CMML) as an early form of CMML. However, the clinical validity of these changes remains uncertain without incorporating biological and genomic factors. In this study, we analyzed a cohort of 911 patients (249 with OM-CMML, 359 with overt CMML, and 303 with myelodysplastic syndromes) using unsupervised clustering to evaluate the role of genomic determinants in refining CMML diagnosis. Our findings show that CMML molecular signatures (biallelic TET2 mutations or SRSF2-TET2 comutations) are linked to a distinct transcriptome, monocytic bias, classical monocytosis, and a higher risk of progression to overt CMML in OM-CMML cases. We developed a weighted genomic model and diagnostic workflow showing that combining genomic signatures with bone marrow monocyte frequencies in OM-CMML more accurately predicts progression to overt CMML. These findings support integrating genomic determinants and our clinic-ready diagnostic workflow into the CMML diagnostic framework to improve accuracy.</p><p><strong>Significance: </strong>Through comprehensive clinical and genomic profiling of a large patient cohort, alongside immunophenotypic and transcriptional cellular analyses, this study provides evidence that incorporating genomic determinants into the diagnostic criteria for OM-CMML improves diagnostic accuracy and refines the identification of early-stage CMML, thereby preventing misclassification.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"414-430"},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053590","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}

{"title":"A Phase 2, Open-Label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma.","authors":"Justin M Darrah, Indumathy Varadarajan, Amitkumar Mehta, Jennifer N Saultz, Matthew S McKinney, Monalisa Ghosh, Usama Gergis, Andrew Krueger, Kevin J Galinsky, Girish Bende, Ajeetha Ramachandran, Varsha Sundaresan, Siddha Kasar, Bradley Hupf, Sharon Chen, Leopold Sellner, Reem Karmali","doi":"10.1158/2643-3230.BCD-25-0323-A","DOIUrl":"10.1158/2643-3230.BCD-25-0323-A","url":null,"abstract":"<p><p>In relapsed/refractory large B-cell lymphoma (LBCL), chimeric antigen receptor (CAR)-natural killer (NK) cell therapies offer potential advantages over CAR-T-cell therapies, including off-the-shelf availability and scalable manufacturing. We performed a phase 2 study of single-dose TAK-007, a cryopreserved, cord blood-derived, off-the-shelf CD19 CAR-NK cell therapy, in 26 heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Adverse events were manageable, with limited grade 1-2 cytokine release syndrome (11.5%). Overall response rate with TAK-007 800 x106 CD19 CAR+ viable NK cells (n=14) was 60.9% (95% CI: 38.5-80.3). Median progression-free survival was 2.0 months (95% CI: 0.99-3.58) in LBCL (n=10) and 5.6 months (95% CI: 1.05-8.57) in indolent NHL (n=7) expansion cohorts. Deep molecular responses, including ctDNA-negative responses, were achieved. Not all TAK-007 products elicited clinical responses; single cell RNA-sequencing showed NK proliferating and NK-CD56dim cell enrichment in TAK-007 products eliciting/not eliciting responses, respectively, which could inform product selection.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717860","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}

{"title":"CAR-NK Cells in B-cell Lymphoma: A New Frontier toward Accessible and Scalable Cellular Therapy.","authors":"Rémy Duléry, Karl-Johan Malmberg, Rizwan Romee","doi":"10.1158/2643-3230.BCD-26-0086","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-26-0086","url":null,"abstract":"<p><p>In this phase II study, TAK-007, an off-the-shelf allogeneic CD19 CAR NK-cell therapy expressing IL-15, demonstrates encouraging response rates, rapid treatment availability, and an excellent safety profile in heavily pretreated B-cell lymphoma, including post-CAR-T patients, albeit with limited durability. These findings, supported by integrated translational analyses, provide important mechanistic insights into CAR-NK biology that may guide future optimization and bring this approach closer to broader clinical application. See related article by Darrah et al., p. XX .</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"OF1-OF4"},"PeriodicalIF":11.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717839","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}

{"title":"No BCMA? No Problem: A CD70-Targeting CAR-NK Cell Shows Promise in High-risk Myeloma.","authors":"Don M Benson, Michael A Caligiuri","doi":"10.1158/2643-3230.BCD-25-0394","DOIUrl":"10.1158/2643-3230.BCD-25-0394","url":null,"abstract":"<p><p>Despite recent advances, multiple myeloma remains essentially incurable for most patients, particularly those with high-risk cytogenetics and those whose disease relapses after BCMA-targeting therapies. A novel CD27 CAR_sIL15 NK cell targeting CD70 may offer new hope in this area of urgent, unmet medical need. See related article by Lin et al., p. 234.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"166-167"},"PeriodicalIF":12.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795030","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}