Blood advances最新文献

{"title":"Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia.","authors":"Andrew R Branagan, Clifton Mo, Matthew Lei, Joshua N Gustine, Andrew J Yee, Elizabeth O'Donnell, Jorge J Castillo, Omar Nadeem, Catherine Flynn, Zachary Bernstein, Rie Nakamoto-Matsubara, Kirsten Meid, Rakesh Verma, Zachary R Hunter, Maria L Guerrera, Galit Alter, Jill Burke, Cynthia Harrington, Emerentia Agyemang, Marilyn Gammon, Kathleen Lively, Lisette Packer, Nora Horick, Jacob Laubach, Constantine S Mitsiades, Nikhil Munshi, Kenneth C Anderson, Steven P Treon, Paul G Richardson, Noopur S Raje, Shayna R Sarosiek","doi":"10.1182/bloodadvances.2025016513","DOIUrl":"10.1182/bloodadvances.2025016513","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with multiple myeloma (MM) and Waldenström macroglobulinemia (WM) have increased risk of severe coronavirus disease 2019. Impaired humoral responses to the primary vaccination series against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in patients with MM and WM, but the impact of booster vaccinations and functional status of the elicited antibodies are unknown. We performed a prospective cohort study investigating SARS-CoV-2 vaccination in patients with MM (n = 93) and WM (n = 48). The primary end point was effective immune response (EIR) at 28 days after the primary vaccination series (ie, anti-spike SARS-CoV-2 antibody titer >250 U/mL). The EIR rate after the primary vaccination series was 47% and 25% in patients with MM and WM, respectively. After the first and second booster vaccinations, the EIR rates increased to 84% and 91% in patients with MM and 60% and 89% in those with WM, respectively. Factors associated with lower EIR in patients with MM were hypogammaglobulinemia, lymphopenia, and treatment with anti-CD38 monoclonal antibody or corticosteroid. In patients with WM, treatment with a Bruton tyrosine kinase inhibitor or rituximab was associated with a lower EIR, whereas asymptomatic and treatment-naïve patients had a higher EIR. Functional profiling identified reduced antibody-dependent cellular phagocytosis, neutrophil phagocytosis, and natural killer cell activity against wild-type and variant SARS-CoV-2 (Alpha, Beta, and Gamma) in patients with MM and WM compared to healthy donors. Our data demonstrate that although patients with MM and WM have impaired humoral responses to the primary SARS-CoV-2 vaccination series, repeated booster vaccines significantly improve immunogenicity. This trial was registered at www.ClinicalTrials.gov as #NCT04830046.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4568-4579"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233242","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":"Deleting ACC1 in platelets alters phospholipidome and reduces platelet activation and thrombosis in mice.","authors":"Marie Octave, Laurence Pirotton, Emma de Cartier d'Yves, Alice Marino, Jérôme Ambroise, Martin Giera, Bruno Guigas, Audrey Ginion, Valentine Robaux, Marijke Kuijpers, Constance Baaten, Johan W M Heemskerk, Zoltan Nagy, Yotis Senis, Davide Brusa, Caroline Bouzin, Luc Bertrand, Christophe Beauloye, Sandrine Horman","doi":"10.1182/bloodadvances.2025015796","DOIUrl":"10.1182/bloodadvances.2025015796","url":null,"abstract":"<p><strong>Abstract: </strong>This study uncovers the pivotal role of acetyl-CoA carboxylase 1 (ACC1) in regulating platelet lipid composition, bioenergetics, activation, and thrombus formation, as demonstrated using a targeted glycoprotein Ibα (GPIbα)-Cre+/- mouse model. By comparing platelet-specific ACC1 knockout mice (GPIbα-Cre+/- × ACC1flx/flx) with both GPIbα-Cre+/- and ACC1flx/flx control groups, we showed that ACC1 deficiency profoundly reshaped the platelet phospholipidome. Specifically, ACC1 deletion led to decreased levels of arachidonic acid-containing phosphatidylethanolamine plasmalogens, thereby limiting thromboxane A2 synthesis, dense granule secretion, and platelet activation upon agonist stimulation. Bioenergetic analysis of ACC1-deficient platelets revealed reduced glycolytic activity, potentially worsening their activation defects. Notably, ACC1 deficiency also enhanced the mitochondrial reserve respiratory capacity, without altering basal respiration or adenosine triphosphate turnover. This increased reserve respiratory capacity correlated with reduced phosphatidylserine exposure, suggesting lower procoagulant activity. Importantly, we showed that ACC1 deficiency impaired thrombus formation without compromising hemostasis. Together, these findings identified ACC1 as a critical regulator of platelet function and highlighted its potential as a target for innovative antithrombotic therapies.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4553-4567"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559210","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":"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 A Diniz, Noboru Asada, Francis 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":"10.1182/bloodadvances.2025016233","url":null,"abstract":"<p><strong>Abstract: </strong>Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 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 < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .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 = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4640-4653"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496244/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib plus rituximab vs ibrutinib monotherapy in patients with Waldenström macroglobulinemia: a pooled analysis.","authors":"Alberto Guijosa, Andres Ramirez-Gamero, Shayna Sarosiek, Andrew R Branagan, Gottfried von Keudell, Steven P Treon, Jorge J Castillo","doi":"10.1182/bloodadvances.2025016536","DOIUrl":"10.1182/bloodadvances.2025016536","url":null,"abstract":"<p><strong>Abstract: </strong>Ibrutinib (I) and ibrutinib plus rituximab (I+R) are highly efficacious in treating Waldenström macroglobulinemia (WM). However, the benefit of adding rituximab remains unclear, and a prospective trial to compare these two regimens has not been undertaken. Therefore, we performed a pooled analysis of prospective studies to compare their effectiveness. Patient-level demographic, response, and survival data were pooled from three prospective studies (ClinicalTrials.gov identifiers: NCT01614821, NCT02604511, NCT02165397). We included patients treated with I+R or I, excluding those without MYD88 mutations. Among 174 patients (58 I+R, 116 I), very good partial response (VGPR) rates were comparable across treatment groups (38% I+R vs 28% I; P = .21). The 48-month progression-free survival (PFS) rate was 74% with I+R vs 61% with I (P = .22). The 48-month overall survival rate was 94% vs 89% (P = .45). In patients with CXCR4 mutations, I+R trended toward higher VGPR (27% vs 11%; P = .10), and had a superior 48-month PFS rate (72% vs 43%; P = .03). CXCR4 mutations were associated with inferior VGPR (42% vs 17%; P = .001) and 48-month PFS in the I arm (43% vs 72%; P = .002). In the I+R arm, CXCR4 mutations were associated with numerically inferior VGPR (47% vs 27%; P = .12), but the 48-month PFS rate was not impacted (74% vs 72%; P = .96). I+R significantly improved PFS over I in patients with CXCR4-mutated WM, along with a nonsignificant increase in VGPR in this subgroup. These results support routine CXCR4 testing in patients with WM, and clinical trials of rituximab with covalent or noncovalent Bruton tyrosine kinase inhibitors.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4705-4715"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658487","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":"TRANSCAR: real-world outcomes of CD19 CAR T-cell therapy in relapsed/refractory transformed indolent lymphomas.","authors":"Pierre Stephan, Roberta Di Blasi, Louise Roulin, Jean Galtier, Julien Calvani, Véronique Meignin, Marie Donzel, Alexandra Traverse-Glehen, Elsa Poullot, Marie Parrens, Vivien Dupont, Alexandra Marquet, Steven Le Gouill, Roch Houot, Francois-Xavier Gros, François Lemonnier, Emmanuel Bachy, Catherine Thieblemont, Pierre Sesques","doi":"10.1182/bloodadvances.2025015834","DOIUrl":"10.1182/bloodadvances.2025015834","url":null,"abstract":"<p><strong>Abstract: </strong>Anti-CD19 chimeric antigen receptor (CAR) T cells have shown impressive results in the treatment of relapsed/refractory aggressive large B-cell lymphomas (LBCLs). However, the prognostic value of the LBCL histological subtype in the context of CAR T-cell therapy is unclear. Here, we report the prognostic value of transformed indolent non-Hodgkin lymphoma (TriNHL; N = 110) confirmed by an expert pathological review (LYMPHOPATH) vs de novo LBCL (N = 391) in the context of CAR T-cell therapy from 4 centers of the French DESCAR-T registry. After 1:1 propensity score matching (n = 170, 85 patients with TriNHL and 85 patients with de novo LBCL), the median follow-up was 19.4 months (95% confidence interval [CI], 12.0-25.1) for patients with TriNHL and 18.5 months (95% CI, 13.8-24.8) for patients with LBCL. The 1-year progression-free survival rate was significantly better (55.8%; 95% CI, 43.6-66.4) in the TriNHL group than in the de novo LBCL group (31.7%; 95% CI, 21.4-42.6; hazard ratio, 0.54; 95% CI, 0.36-0.82; P = .0034). The best overall response rate and complete response rate were 82.4% and 63.5%, respectively, whereas they were 63.5% and 50.6%, respectively, for the TriNHL group compared with the de novo LBCL group. The 1-year overall survival was also longer in the TriNHL group than in the de novo LBCL group (72.1%, [95% CI, 59.6-81.4] vs 50.7%, [95% CI, 38.2-62.0]; P = .031). Similar findings were found via an inverse probability weighting statistical approach. No difference was observed in terms of toxicity. In conclusion, our matched-comparison study revealed a greater efficacy of CAR T-cell therapy, with a toxicity profile for patients with TriNHL comparable with that for patients with LBCL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4693-4704"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962992","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":"Genetic variation at PPM1H predicts mobilization efficiency in stem cell donors.","authors":"Yen Phuong La, Daniela Torres Di Bello, Maria Laura Mahecha Escobar, Caterina Cafaro, Stina Wichert, Aitzkoa Lopez de Lapuente Portilla, Björn Nilsson","doi":"10.1182/bloodadvances.2024015246","DOIUrl":"10.1182/bloodadvances.2024015246","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4683-4686"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612100","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":"A standardized metric to define a successful transition from pediatric to adult care in sickle cell disease.","authors":"Galia Pollock, Susanna Curtis","doi":"10.1182/bloodadvances.2025017088","DOIUrl":"10.1182/bloodadvances.2025017088","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 18","pages":"4622-4623"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032797","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":"Elucidating the dynamics of integrin αIIbβ3 from native platelet membranes by cryo-EM with build-and-retrieve method.","authors":"Xu Han, Zhemin Zhang, Chih-Chia Su, Meinan Lyu, Masaru Miyagi, Edward Yu, Marvin T Nieman","doi":"10.1182/bloodadvances.2025016209","DOIUrl":"10.1182/bloodadvances.2025016209","url":null,"abstract":"<p><strong>Abstract: </strong>Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that affect the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible to obtain atomic-level-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the \"build-and-retrieve\" (BaR) data processing methodology. We applied this iterative bottom-up methodology on resting human platelet membranes for an in-depth systems biology approach to uncover how lipids, metal binding, post-translational modifications, and cofactor associations in the native environment regulate platelet function at the molecular level. Here, we report using cryo-EM followed by the BaR method to solve the unmodified integrin αIIbβ3 structure directly from resting human platelet membranes in its inactivated and intermediate states at 2.75 and 2.67 Å, respectively. Furthermore, we also solved a novel dimer conformation of αIIbβ3 at 2.85 Å formed by 2 intermediate states of αIIbβ3. This may indicate a previously unknown self-regulatory mechanism of αIIbβ3 in its native environment. In conclusion, our data show the power of using cryo-EM with the BaR method to determine 3 distinct structures including a novel dimer directly from natural sources. This approach allows us to identify unrecognized regulation mechanisms for proteins without artifacts owing to purification processes. These data have the potential to enrich our understanding of platelet signaling circuitry.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4592-4606"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233238","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":"Maintenance therapy with romidepsin after autologous stem-cell transplant for peripheral T-cell lymphoma.","authors":"Niloufer Khan, Parastoo B Dahi, Farhad Khimani, Andrei R Shustov, Mazyar Shadman, Jia Ruan, Alison J Moskowitz, Andrew D Zelenetz, Ariela Noy, David J Straus, Pamela Drullinsky, Audrey Hamilton, Anita Kumar, Craig S Sauter, Gunjan L Shah, Matthew J Matasar, Esther Drill, Theresa Davey, Helen Hancock, Nivetha Ganesan, Natasha Galasso, Koen van Beisen, Sergio Giralt, Steven M Horwitz","doi":"10.1182/bloodadvances.2024014263","DOIUrl":"10.1182/bloodadvances.2024014263","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with peripheral T-cell lymphoma (PTCL) have suboptimal outcomes. Autologous hematopoietic stem-cell transplantation (AHCT) is a therapeutic strategy for patients in first complete remission (CR1) or first partial remission (PR1), with median intent-to-treat progression-free survival (PFS) of 36% to 48%. Romidepsin is a histone deacetylase inhibitor used for treatment of relapsed/refractory PTCL. We present a multicenter study to evaluate the PFS of patients receiving maintenance therapy with romidepsin after AHCT. Twenty-six patients who underwent AHCT in CR1 or PR1 were evaluated for the primary end point of 2-year PFS. The exploratory cohort enrolled patients who underwent transplantation during or after CR/PR2 (n = 5) or high-risk histologies (n = 2). Patients underwent AHCT with carmustine, etoposide, cytarabine, and melphalan conditioning. Romidepsin 14 mg/m2 was started on days 42 to 80 after -AHCT every other week until 6 months of -AHCT, every 3 weeks between 6 months and 1-year of -AHCT, and every 4 weeks between 1 and 2 years of -AHCT. PFS was estimated using the Kaplan-Meier analysis. Forty-seven patients consented and 13 did not receive romidepsin. With a median progression-free follow-up of 32 months (range, 24-36), 15 of the first 25 patients in cohort 1 were progression-free after 2 years. The estimated 2-year PFS was 62% (95% confidence interval, 45-83). The most common toxicities were fatigue (n = 24, 73%), decreased platelets (n = 16, 48%), and anemia (n = 16, 48%). Although the study did not meet its desired primary efficacy end point, maintenance romidepsin was feasible, with a favorable estimated 2-year PFS of 62%. This trial was registered at www.ClinicalTrials.gov as #NCT01908777.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4687-4692"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779167","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":"Immunoglobulin prophylaxis should be initiated after bispecific antibody therapy in multiple myeloma, regardless of IgG levels.","authors":"Rahul Banerjee, Meera Mohan, Kai Rejeski, Benjamin R Puliafito, Diana D Cirstea, Gurbakhash Kaur, Shonali Midha, Georgia J McCaughan, Nikhil M Kumar, Nikita Mehra, Bhausaheb Bagal, Noopur S Raje","doi":"10.1182/bloodadvances.2025016490","DOIUrl":"10.1182/bloodadvances.2025016490","url":null,"abstract":"<p><strong>Abstract: </strong>Bispecific antibodies (bsAbs), such as teclistamab, elranatamab, linvoseltamab, and talquetamab, have impressive efficacy in multiple myeloma (MM) but come with substantial infectious risks that do not dissipate over time. Immunoglobulin replacement therapy (IgRT), which includes IV and subcutaneous (SC) immunoglobulins, may lower these risks. In this viewpoint, we contrast primary IgRT prophylaxis (initiation regardless of IgG levels) with preemptive IgRT treatment (initiation only once IgG levels fall below a certain threshold) in this setting. We make evidence-based arguments for primary prophylaxis as a safer and simpler approach than preemptive IgG-guided IgRT. We also discuss strategies to improve the cost-effectiveness of IV and SC immunoglobulins across the world. Given the overwhelmingly favorable benefit-risk profile of IgRT, coupled with the limitations inherent to IgG measurements in MM, withholding IgRT access based on arbitrary IgG thresholds is neither scientifically sound nor clinically appropriate for patients with MM who are receiving bsAb therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4720-4726"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681974","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}