Blood advances最新文献

{"title":"Comparative Infection Risk in CAR T vs Bispecific Antibodies in B cell Lymphoma: A Systematic Review and Meta-Analysis.","authors":"Herman J van Besien, Neela Easwar, Michelle Demetres, Michelle Pasciolla, Tsiporah Shore, John P Leonard, Juliet Barker, Peter Martin, Samuel Yamshon","doi":"10.1182/bloodadvances.2025016291","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016291","url":null,"abstract":"<p><p>CD3xCD20 bispecific antibody (BsAb) therapy and CD19 directed chimeric antigen receptor (CAR) T cell therapy are novel immunotherapies that have shown impressive efficacy in B cell lymphomas but also come with significant morbidity and mortality, including infections. This meta-analysis compares rates of infections between commercially approved CAR T and bispecific antibody therapy in patients with B cell lymphomas (B-NHL). We conducted a systematic review for prospective trials assessing commercially approved CAR T and BsAbs in patients with B-NHL. Twenty-five studies comprising 3202 patients were included in the analysis. We used random effects models to evaluate all grade infections, grade 3+ infections, and infection-related mortality, calculating both pooled rates per patient and per patient-month. While CAR T and BsAbs had similar rates of all grade infections per patient (0.44 vs 0.54; p = 0.18), BsAbs had a higher rate of infection per patient-month (0.0397 vs 0.0167; p = 0.0012). Similarly, CAR T and BsAbs had similar rates of grade 3+ infections per patient (0.16 vs 0.22; p = 0.08) while BsAbs had a higher rate of grade 3+ infections per patient-month (0.0165 vs 0.0069; p = 0.0003). CAR T and BsAbs products had similar rates of infection-related mortality per patient (0.04 vs 0.03; p = 0.26) and per patient-month (0.0023 vs 0.0022, p = 0.96). Our findings point to the potential increased burden of infections over time in patients receiving BsAb therapy, particularly for patients on indefinite therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538952","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}

{"title":"Prospective Cohort Study of eDiary Acute Pain Assessments in Sickle Cell Disease During Third Trimester and Postpartum.","authors":"Eugenia Vicky Asare, William Kwesi Ghunney, John Benaiah Ayete-Nyampong, Enoch Alabi Mensah, Alim Swarray-Deen, Edeghonghon Olayemi, Theodore Kobla Boafor, Jude Jonassaint, Charles R Jonassaint, Mark Rodeghier, Samuel Antwi Oppong, Michael R DeBaun","doi":"10.1182/bloodadvances.2024015750","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015750","url":null,"abstract":"<p><p>Pregnant women with sickle cell disease (SCD) are at higher risk of SCD-related morbidity and mortality compared to after pregnancy. Existing data from healthcare utilization suggest increased acute vaso-occlusive pain events during pregnancy, particularly in the 3rd trimester and puerperium (6 weeks after childbirth). Many acute vaso-occlusive pain events are managed at home and may not capture the full scope of pregnancy-related morbidity. To date, no studies have examined daily self-reported acute vaso-occlusive pain events during pregnancy and after pregnancy to assess their occurrence at home. Based on self-report using an eDiary mobile application, we tested the primary hypothesis that self-reported acute SCD pain events during pregnancy (3rd trimester to puerperium) are greater than after pregnancy (beginning of 6 to end of 9 months after childbirth).In a tertiary care hospital in Ghana, we approached 42 pregnant women with SCD ≤16 weeks gestation to participate in the prospective study; 95.2% (40/42) of pregnant women with SCD agreed to participate; only 33 participants completed 71.5% of expected eDiary mobile application entries during and after pregnancy. The eDiary data revealed a 1.85-fold higher self-reported acute SCD pain incidence rate during pregnancy compared to after pregnancy (0.74 vs. 0.40 events per person-month; p<0.001).</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538958","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}

{"title":"Refinement of Day 28 Treatment Response Criteria for Acute GVHD: A Collaboration Study of the JSTCT and MAGIC.","authors":"Yu Akahoshi, Yoshihiro Inamoto, Nikolaos Spyrou, Hideki Nakasone, Marcio Diniz, Noboru Asada, Francis Ayuketang Ayuk, Hannah K Choe, Noriko Doki, Tetsuya Eto, Aaron M Etra, Elizabeth O Hexner, Nobuhiro Hiramoto, William J Hogan, Ernst Holler, Keisuke Kataoka, Toshiro Kawakita, Masatsugu Tanaka, Takashi Tanaka, Naoyuki Uchida, Ingrid Vasova, Satoshi Yoshihara, Fumihiko Ishimaru, Takahiro Fukuda, Yi-Bin Chen, Junya Kanda, Ryotaro Nakamura, Yoshiko Atsuta, James L M Ferrara, Yoshinobu Kanda, John E Levine, Takanori Teshima","doi":"10.1182/bloodadvances.2025016233","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016233","url":null,"abstract":"<p><p>Overall response (OR) that combines complete (CR) and partial responses (PR) at day (D) 28 is the conventional endpoint for acute GVHD trials. Since PR includes heterogeneous clinical presentations, reclassifying PR could produce a better endpoint. Patients in the primary treatment cohort from JSTCT were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated D28 refined response (RR) criteria based on symptoms at treatment and D28. We then compared RR for primary and second-line treatments to conventional criteria, using the area under the receiver operating curve (AUC) and negative predictive value (NPV) for 6-month non-relapse mortality as performance measures. RR considered patients with grade 0/I at D28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC: 0.73 vs. 0.69, P<0.001; NPV: 92.0% vs. 89.6%, P<0.001) and MAGIC (AUC: 0.71 vs. 0.68, P=0.032; NPV: 90.9% vs. 89.8%, P=0.009). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC: 0.64 vs. 0.63, P=0.775; NPV: 74.5% vs. 66.0%, P<0.001) and MAGIC (AUC: 0.67 vs. 0.64, P=0.105; NPV: 86.8% vs. 76.1%, P=0.004). Classifying persistent, but mild skin symptoms as responses and residual lower GI GVHD as non-responses were major drivers in improving the prognostic performance of RR. Our externally validated D28 RR would serve as a better endpoint than conventional criteria in future first- and second-line treatment trials.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538960","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}

{"title":"R-CHOP and R-cytarabine for transplant-ineligible MCL.","authors":"Pavel Klener, Liliana Tušková, Petra Blahovcová, Marek Trněný","doi":"10.1182/bloodadvances.2025016373","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016373","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538959","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}

{"title":"Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies.","authors":"Andrew Kowalski, Jillian Lykon, Benjamin T Diamond, David G Coffey, Marcella Kaddoura, Francesco Maura, James E Hoffman, Abhishek Pandey, Dickran Kazandjian, Carl Ola Landgren","doi":"10.1182/bloodadvances.2025016911","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016911","url":null,"abstract":"<p><p>Bispecific antibodies for treatment for multiple myeloma are highly effective but commonly cause cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Emerging data indicate that prophylactic tocilizumab may reduce CRS, without impacting efficacy. We administered a single dose of tocilizumab prior to the first dose of bispecific antibodies to 119 patients to determine the impact on CRS in a real-world setting including BCMAxCD3- and GPRC5DxCD3-targeted antibodies. The best overall response rate (ORR) was 65.7% (binomial 95%CI: 55.8%-74.7%). We observed a low overall rate of CRS (10.1%: 5.3%-17%). For teclistamab, elranatamab, linvoseltamab and talquetamab individually, the CRS rate was 8.9%, 12.5%, 0%, and 13%. The overall ICANS (5.9%: 2.4%-11.7%) was low, but similar to rates without prophylactic tocilizumab. CRS was limited to grade 1 for 10 of 12 events. There were no grade 3 CRS events, and no additional doses of tocilizumab or corticosteroids were given for CRS. Our real-world evidence results suggest that tocilizumab may be effective as a preventative, rather than reactive, measure to prevent CRS without compromising efficacy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538962","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}

{"title":"Effect of age on ISTH-BAT scores and Low VWF diagnosis in the Zimmerman Program.","authors":"Ferdows Atiq, Pamela A Christopherson, Dearbhla Doherty, Anne-Marije Hulshof, Sandra L Haberichter, Veronica H Flood, Michelle Lavin, Niamh M O'Connell, Kevin Ryan, Mary B Byrne, Julie Grabell, Paula D James, David Lillicrap, Robert R Montgomery, Jorge Di Paola, James S O'Donnell","doi":"10.1182/bloodadvances.2025016725","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016725","url":null,"abstract":"<p><p>An essential component of Low VWF / type 1 VWD diagnosis is to identify patients with an increased bleeding phenotype, as most individuals with VWF levels in the 30-50 IU/dL range do not bleed. The ISTH-BAT, a widely used tool for assessing bleeding severity, has recently been shown to be age-dependent. While age may also influence ISTH-BAT scores in individuals with VWF levels between 30-50 IU/dL and subsequently affect Low VWF diagnosis, this relationship has not been investigated. Therefore, we analyzed 325 participants from the Zimmerman Program, of whom 220 (67.7%) had abnormal ISTH-BAT scores, while 105 (32.3%) had normal scores. Our analysis demonstrates that age critically influences the likelihood of attaining an abnormal ISTH-BAT score and thus being registered with a formal diagnosis of Low VWF /type 1 VWD. For example, if children are first assessed at ³ 10 years, they are twice as likely to have an abnormal ISTH-BAT compared to those first investigated < 10 years (p<0.001). Additionally, the prevalence of abnormal ISTH-BAT scores was significantly higher in women aged ≥44 years (91.8%) compared to women aged 18-28 years (66.7%; p=0.004). Finally, we demonstrate that the change in abnormal ISTH-BAT threshold at the age of 18 critically impacts Low VWF diagnosis, due to lower rates of abnormal ISTH-BAT scores in young adults (p=0.006). In conclusion, we demonstrate that the likelihood of a Low VWF / type 1 VWD diagnosis is influenced by the age at which ISTH-BAT is first assessed in individuals with mild-to-moderately reduced VWF levels.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538954","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}

{"title":"Dose-Reduced Apixaban for Secondary Prophylaxis in Severely Obese Patients: A Single Center Analysis.","authors":"Eliot A Rapoport, Noelle W Townsend, Nadine Farhat, Parth Patel, Henny H Billett","doi":"10.1182/bloodadvances.2025016037","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016037","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538953","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}

{"title":"Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia.","authors":"Mark J Levis, Mehdi Hamadani, Brent R Logan, Richard J Jones, Anurag K Singh, Mark R Litzow, John R Wingard, Esperanza B Papadopoulos, Alexander E Perl, Robert J Soiffer, Celalettin Ustun, Masumi Ueda Oshima, Geoffrey L Uy, Edmund K Waller, Sumithira Vasu, Melhem M Solh, Asmita Mishra, Lori S Muffly, Hee-Je Kim, Matthias Stelljes, Yuho Najima, Masahiro Onozawa, Kirsty J Thomson, Caroline Chen, Nahla Hasabou, Matt Rosales, Jason E Hill, Stanley C Gill, Rishita Nuthethi, Denise King, Adam M Mendizabal, Steven M Devine, Mary M Horowitz, Yi-Bin Chen","doi":"10.1182/bloodadvances.2025016306","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016306","url":null,"abstract":"<p><p>We conducted a post-hoc analysis of data from BMT CTN 1506 (MORPHO), a randomized trial of gilteritinib versus placebo as post-transplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 co-mutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD-negative pre-HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC versus RIC. NPM1 co-mutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. Only in participants who were NPM1 wild-type at diagnosis and were FLT3-ITD MRD-positive prior to HCT did MAC appear superior to RIC in preventing relapse. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from myeloablative conditioning, and that, much like AML therapy prior to HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. (NCT02997202).</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538956","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}

{"title":"Therapeutic Innovations in Hemophilia: The Essential Role of a Positive Reinvestment Cycle.","authors":"Cedric Hermans, Glenn F Pierce","doi":"10.1182/bloodadvances.2025016497","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016497","url":null,"abstract":"<p><p>Hemophilia stands out among rare genetic diseases for its significant therapeutic advancements, closely tied to substantial financial investments. Key factors driving this progress include severe hemorrhagic consequences from an early age, its impact on royal families, the HIV and hepatitis C contamination tragedies, the identification of FVIII and FIX genes, and advancements in biotechnology. Maintaining low, measurable concentrations of FVIII or FIX in the blood has proven pivotal in improving patient outcomes. The mobilization of the global hemophilia community, led by the World Federation of Hemophilia (WFH), the European Association for Haemophilia and Allied Disorders (EAHAD) and the National Bleeding Disorder Foundation (NBDF), has continuously advocated for access to safe, effective treatments. With reinvestments from biopharmaceutical partners, revolutionary options, including gene therapy, have emerged. However, this cycle of innovation and investment, essential for curing all patients worldwide, faces potential threats. This article aims to highlight the critical importance of investing in hemophilia treatment and research, a topic of concern for all stakeholders within the hemophilia community.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538961","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}

{"title":"Efficacy and Safety of BCMA Nanobody CAR-T Cell Therapy in Relapsed or Refractory Plasma Cell Myeloma.","authors":"Xian Zhang, Lin Wang, Junfang Yang, Xiaona Hu, Hui Wang, Lina Zhang, Xiaoge Zhou, Ying Liu, Qinglong Wang, Peihua Lu","doi":"10.1182/bloodadvances.2025016322","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016322","url":null,"abstract":"<p><p>BCMA CAR-T has demonstrated promising therapeutic efficacy in refractory and relapsed multiple myeloma. However, distinct CAR-T constructs exhibit varying therapeutic outcomes. As the antigen recognition domain, nanobodies offer a small, stable, single-domain structure with enhanced affinity and specificity compared to conventional scFv fragments. We explored the use of nanobody-based BCMA(S103) CAR-T cell therapy for R/R plasma cell myeloma (NCT04447573). The CAR construct incorporates dual nanobody VHHs targeting BCMA (dVHHs). A cohort of 27 patients was treated with S103 CAR-T therapy, which included four cases of plasma cell leukemia, One case of anaplastic plasma cell myeloma. 11 cases had multiple extramedullary lesions. 11 patients exhibited high-risk genetic abnormalities, including 4 with TP53 mutations. One month after CAR-T infusion, the overall response rate (ORR) was 96.3% (26/27), with a CR)+ VGPR rate of 59.2% (16/27). At the three-month follow-up, the ORR increased to 100% (27/27), with a CR+VGPR rate of 81.5% (22/27). The median duration of remission was 11 months ( 2-36 months). The one-year OS rate was 61.1%, and PFS was 57.2%. Conclusion: BCMA CAR-T therapy, utilizing dual nanobody VHHs targeting BCMA, demonstrates a high overall response rate (ORR) and manageable safety profile in treating patients with R/R plasmacytic myeloma, including those with high-risk features such as extramedullary lesions, high-risk cytogenetic abnormalities, plasma cell leukemia, or anaplastic plasmacytoma.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504859","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}