Nadia Peragine, Michela Ansuinelli, Giulia Radice, Mariangela Di Trani, Maria Stefania De Propris, Giada Almici, Marina Parisi, Maria Paola Martelli, Daniele Mattei, Erika Borlenghi, Federico Fazio, Daniele Vallisa, Sabina Chiaretti, Anna Guarini, Robin Foà
{"title":"Dynamics of in vivo immune remodeling in Ph<sup>+</sup> all patients receiving frontline ponatinib and blinatumomab therapy.","authors":"Nadia Peragine, Michela Ansuinelli, Giulia Radice, Mariangela Di Trani, Maria Stefania De Propris, Giada Almici, Marina Parisi, Maria Paola Martelli, Daniele Mattei, Erika Borlenghi, Federico Fazio, Daniele Vallisa, Sabina Chiaretti, Anna Guarini, Robin Foà","doi":"10.1038/s41408-026-01595-8","DOIUrl":"10.1038/s41408-026-01595-8","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711349","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}
JE Wiedmeier-Nutor, DL Riggs, CK Stein, KK Mangalaparthi, RK Kandasamy, S. Brown, K. Franke, Y. Shotts, JC Figueroa Aguirre, YW Asmann, E. Braggio, R. Fonseca, A. Pandey, M. Chesi, PL Bergsagel
{"title":"Establishment and characterization of multiple myeloma cell lines from a single patient’s disease course immortalizes clonal heterogeneity","authors":"JE Wiedmeier-Nutor, DL Riggs, CK Stein, KK Mangalaparthi, RK Kandasamy, S. Brown, K. Franke, Y. Shotts, JC Figueroa Aguirre, YW Asmann, E. Braggio, R. Fonseca, A. Pandey, M. Chesi, PL Bergsagel","doi":"10.1038/s41408-026-01597-6","DOIUrl":"https://doi.org/10.1038/s41408-026-01597-6","url":null,"abstract":"Multiple myeloma (MM) is an incurable plasma cell neoplasm characterized by diverse and complex genetic abnormalities, including translocations of immunoglobulin (Ig) genes and a hyperdiploid karyotype. Much of our current understanding of MM genetics, epigenetics, pathogenesis and response/resistance to myeloma directed therapies originated from studies on human MM-derived cell lines (HMCL). In this study, we conducted an integrated multi-omics analysis in five hyperdiploid cell lines established from serial samples from a single relapsed/refractory hyperdiploid MM patient, enabling detailed characterization of the genetic landscape and molecular alterations through disease progression.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"6 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728874","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}
Ferran Balbastre-Úbeda, Sara Torres-Esquius, Maria Gabarrós-Subirà, Francisco Beas, Jordi Leno-Colorado, Cristina Sanchez-Morales, Tzu Hua Chen-Liang, Susana Urban-Giral, Meritxell Tena-Alegre, Ana María Hurtado, María Jesús Casas-Tio, Ana María Garrido, Pamela Acha, Adoración Blanco, Francesc Solé, Mónica Del Rey, María Díez-Campelo, David Valcárcel, Maria Julia Montoro, Andrés Jerez
{"title":"Hair bulb and oral mucosa DNA for prompt germline testing in hematologic neoplasms.","authors":"Ferran Balbastre-Úbeda, Sara Torres-Esquius, Maria Gabarrós-Subirà, Francisco Beas, Jordi Leno-Colorado, Cristina Sanchez-Morales, Tzu Hua Chen-Liang, Susana Urban-Giral, Meritxell Tena-Alegre, Ana María Hurtado, María Jesús Casas-Tio, Ana María Garrido, Pamela Acha, Adoración Blanco, Francesc Solé, Mónica Del Rey, María Díez-Campelo, David Valcárcel, Maria Julia Montoro, Andrés Jerez","doi":"10.1038/s41408-026-01602-y","DOIUrl":"10.1038/s41408-026-01602-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711347","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}
Naroa Barrena, Edurne San José-Enériz, Luis V. Valcárcel, Danel Olaverri-Mendizabal, Estibaliz Urizar-Compains, Leire Garate, Estíbaliz Miranda, Paula Rodriguez-Marquez, Romika Kumari, Patxi San Martín-Uriz, Juan Roberto Rodriguez-Madoz, Leonor Puchades-Carrasco, Caroline A. Heckman, Paula Rodriguez-Otero, Francisco J. Planes, Xabier Agirre, Felipe Prósper
{"title":"A myeloid-dormant metabolic transcriptome identifies a poor-prognosis subgroup in hyperdiploid multiple myeloma with targetable vulnerabilities","authors":"Naroa Barrena, Edurne San José-Enériz, Luis V. Valcárcel, Danel Olaverri-Mendizabal, Estibaliz Urizar-Compains, Leire Garate, Estíbaliz Miranda, Paula Rodriguez-Marquez, Romika Kumari, Patxi San Martín-Uriz, Juan Roberto Rodriguez-Madoz, Leonor Puchades-Carrasco, Caroline A. Heckman, Paula Rodriguez-Otero, Francisco J. Planes, Xabier Agirre, Felipe Prósper","doi":"10.1038/s41408-026-01604-w","DOIUrl":"https://doi.org/10.1038/s41408-026-01604-w","url":null,"abstract":"Aberrant metabolism, a hallmark of cancer, reveals vulnerabilities across human tumors. Here, we demonstrate that transcriptomic alterations of metabolism-related genes (metabolic transcriptome) in multiple myeloma (MM), classify patients into six metabolic-transcriptional groups characterized by specific metabolic pathways and cytogenetic alterations, independent of currently described myeloma risk groups. Interestingly, hyperdiploid patients clustered into 2 groups (MM5 and MM6) with significantly distinct Progression-Free and Overall Survival. The MM5 group, with worse prognosis, showed a significant enrichment in myeloid and dormant cell signatures. Regulon analysis identified myeloid transcription factors (TFs) as regulators of metabolic, myeloid, and dormant genes in MM5. In addition to myeloid genes acting as potential biomarkers and therapeutic targets, the metabolic gene ACSL1 plays a crucial role in MM5, decreasing cell proliferation by affecting metabolism and mitochondrial function, sensitizing MM to BCL-2 family inhibitors. These findings highlight ACSL1 as a promising therapeutic target for MM5 and provide new insights into MM metabolic heterogeneity that may guide future precision medicine strategies.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"67 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728882","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}
Kenneth JC Lim, Melinda Tan, Ricardo Parrondo, Saurabh Chhabra, Christoph Schaefers, Katharine Dooley, Andre De Menezes Silva Corraes, Malvika Gupta, Darin Carabenciov, Morie Gertz, Lisa Hwa, Stephens Haily, Prashant Kapoor, Taxiarchis Kourelis, Rahma Warsame, Joselle Cook, Moritz Binder, Nadine Abdallah, Saurabh Zanwar, P. Leif Bergsagel, Udit Yadav, Erin Wiedmeier-Nutor, Susan Geyer, Sikander Ailawadhi, Rafael Fonseca, Shaji Kumar, Anastasia Zekeridou, Yi Lin
{"title":"Prophylactic dexamethasone at the time of absolute lymphocyte expansion does not mitigate risk or event-free survival for immune effector cell associated delayed neurotoxicity","authors":"Kenneth JC Lim, Melinda Tan, Ricardo Parrondo, Saurabh Chhabra, Christoph Schaefers, Katharine Dooley, Andre De Menezes Silva Corraes, Malvika Gupta, Darin Carabenciov, Morie Gertz, Lisa Hwa, Stephens Haily, Prashant Kapoor, Taxiarchis Kourelis, Rahma Warsame, Joselle Cook, Moritz Binder, Nadine Abdallah, Saurabh Zanwar, P. Leif Bergsagel, Udit Yadav, Erin Wiedmeier-Nutor, Susan Geyer, Sikander Ailawadhi, Rafael Fonseca, Shaji Kumar, Anastasia Zekeridou, Yi Lin","doi":"10.1038/s41408-026-01598-5","DOIUrl":"https://doi.org/10.1038/s41408-026-01598-5","url":null,"abstract":"High post-infusion absolute lymphocyte count (ALC) following ciltacabtagene autoleucel (cilta-cel) therapy is associated with an increased risk of immune effector cell–associated delayed neurotoxicity (IEC-DNT), including parkinsonism (IEC-PKS) and cranial nerve palsies (IEC-NP). Between December 2024 and August 2025, we evaluated a prophylactic strategy using a short course of dexamethasone (DEX) in 57 patients with high-ALC, defined as a post-infusion ALC of ≥3 × 10⁹/L on serial monitoring after CAR-T infusion. DEX was administered at 10 mg twice daily for a minimum of three days. Outcomes were compared with a historical control cohort of 104 patients with high-ALC treated between February 2022 and November 2024. While DEX appeared to attenuate the severity of facial nerve palsy, it did not significantly improve event-free survival for IEC-DNT, IEC-PKS, or IEC-NP, nor did it reduce the severity of IEC-PKS. Analysis of ALC kinetics demonstrated no statistically or biologically meaningful reduction in lymphocyte expansion, suggesting that the dose and duration of dexamethasone may be insufficient, or that additional immune and host factors contribute to the risk of IEC-DNT. These findings highlight the limited role of corticosteroid prophylaxis and underscore the need for more mechanistically targeted strategies to mitigate this challenging complication of BCMA-directed CAR-T therapy.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"9 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728877","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}
Tae Min Kim, Seok Jin Kim, Jin Seok Kim, Deok-Hwan Yang, Dok Hyun Yoon, Won Sik Lee, Eunyoung Lee, Jeong-Ok Lee, Ahmad Hatem Mattour, Jorge Chaves, Bong-Seog Kim
{"title":"Bosmolisib (BR101801), a novel PI3K-δ/γ and DNA-PK inhibitor for relapsed/refractory patients with peripheral T-cell lymphoma: a phase I study","authors":"Tae Min Kim, Seok Jin Kim, Jin Seok Kim, Deok-Hwan Yang, Dok Hyun Yoon, Won Sik Lee, Eunyoung Lee, Jeong-Ok Lee, Ahmad Hatem Mattour, Jorge Chaves, Bong-Seog Kim","doi":"10.1038/s41408-026-01600-0","DOIUrl":"https://doi.org/10.1038/s41408-026-01600-0","url":null,"abstract":"Bosmolisib is a novel triple inhibitor of PI3K-δ/γ and DNA-PK for malignancy treatment. This was a first-in-human, phase 1, open-label, dose-escalation, and dose-expansion trial with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Patients received bosmolisib orally once daily in 28-day cycles across four dose levels (50–325 mg) until disease progression or unacceptable toxicity. The study utilized a 3 + 3 dose-escalation design to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), followed by expansion at RP2D. Primary endpoints were safety and MTD/RP2D determination; secondary endpoints included efficacy, pharmacokinetics, and pharmacodynamics. A total of 26 patients were enrolled in dose-escalation (N = 12) and dose-expansion (N = 14). Median age was 65 years with a median of 3 prior therapies. Bosmolisib demonstrated acceptable tolerability; dose-limiting toxicities were observed at 325 mg (alanine transaminase [ALT] increased and erythema multiforme), establishing MTD/RP2D at 200 mg. Most adverse events (AEs) were Grade 1–2, with the most common Grade ≥3 AEs (ALT 23.1%, aspartate transaminase 15.4%). Of 23 evaluable patients, the overall response rate (ORR) was 26.1%, and in PTCL patients, ORR was 31.6% with one patient achieving a durable complete response. Pharmacodynamics profiling showed statistically significant decrease in regulatory T-cells. These findings support evaluation of bosmolisib in a phase 2 trial (ClinicalTrials.gov number, NCT04018248).","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148693502","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}
Alice X. Wang, Tala Shekarkhand, David Nemirovsky, Andriy Derkach, Carlyn R. Tan, Issam S. Hamadeh, Ross S. Firestone, Eric Jurgens, Kevin Miller, Dhwani Patel, Neha Korde, Alexander M. Lesokhin, Sham Mailankody, Hani Hassoun, Hamza Hashmi, Sridevi Rajeeve, Urvi A. Shah, Kylee Maclachlan, Gunjan L. Shah, Michael Scordo, Heather J. Landau, Sergio A. Giralt, Saad Z. Usmani, Malin Hultcrantz
{"title":"Impact of granulocyte colony-stimulating factors on cytokine release syndrome during bispecific antibody initiation in relapsed/refractory multiple myeloma","authors":"Alice X. Wang, Tala Shekarkhand, David Nemirovsky, Andriy Derkach, Carlyn R. Tan, Issam S. Hamadeh, Ross S. Firestone, Eric Jurgens, Kevin Miller, Dhwani Patel, Neha Korde, Alexander M. Lesokhin, Sham Mailankody, Hani Hassoun, Hamza Hashmi, Sridevi Rajeeve, Urvi A. Shah, Kylee Maclachlan, Gunjan L. Shah, Michael Scordo, Heather J. Landau, Sergio A. Giralt, Saad Z. Usmani, Malin Hultcrantz","doi":"10.1038/s41408-026-01594-9","DOIUrl":"https://doi.org/10.1038/s41408-026-01594-9","url":null,"abstract":"Bispecific antibody (BsAb) treatment in multiple myeloma can be associated with adverse events including cytokine release syndrome (CRS), cytopenias, and infections. While granulocyte colony-stimulating factors (G-CSF) can be used to treat neutropenia, little is known about their safety during the BsAb initiation period and whether G-CSF can increase the risk of CRS. To assess the impact of G-CSF on risk of CRS, we included all patients with multiple myeloma who received at least one dose (step-up doses [SUD] and first treatment dose [FTD]), of commercial teclistamab, elranatamab, or talquetamab between November 2022 and April 2024 at Memorial Sloan Kettering Cancer Center (N = 186). Exposure to G-CSF was defined as administration of at least one dose of filgrastim from 48 h before up to 7 days after BsAb SUD or FTD, or one dose of peg-filgrastim between 7 days prior to up to 7 days after BsAb SUD or FTD. Of the 186 patients, 22 were classified as G-CSF exposed. CRS occurred in 16/22 (73%) patients with G-CSF exposure vs 76/164 (46%) of non-exposed. All CRS was grade 1 (56%) or grade 2 (44%) and the majority occurred prior to G-CSF was given (16/22 patients). The median absolute neutrophil count (ANC) at time of G-CSF exposure was 0.5 × 109/L (0.4–0.7). There was a trend towards increased risk of CRS after G-CSF exposure, although not significant (hazard ratio [HR] 1.7, 95% confidence interval [CI] 0.6–4.7, p = 0.3). These results suggest that G-CSF administration can be considered for neutropenia during BsAb initiation.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148693501","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}
Haley Thigpen, Kendall Diebold, Todd Mudd, Maris Hardee, Manuel Espinoza-Gutarra, Antonio Di Stasi, Donna Salzman, Razan Mohty, Jorge Cortes, Ravi Bhatia, Omer Jamy
{"title":"Post-transplant hypomethylating agents plus venetoclax maintenance improves survival in high-risk myeloid malignancies: A matched cohort study.","authors":"Haley Thigpen, Kendall Diebold, Todd Mudd, Maris Hardee, Manuel Espinoza-Gutarra, Antonio Di Stasi, Donna Salzman, Razan Mohty, Jorge Cortes, Ravi Bhatia, Omer Jamy","doi":"10.1038/s41408-026-01601-z","DOIUrl":"10.1038/s41408-026-01601-z","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683423","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":"Treatment of adult acute lymphoblastic leukemia-a therapeutic revolution in the making.","authors":"Hagop Kantarjian, Ayalew Tefferi","doi":"10.1038/s41408-026-01583-y","DOIUrl":"10.1038/s41408-026-01583-y","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"16 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677025","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}
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