Robyn T. Cohen, Jane S. Hankins, Kirsten K. Ness, Lewis L. Hsu, Tracy Baynard, Amy Tang, Shlomit Radom‐Aizik, Kevin Guerrero, Mark Rodeghier, Robert I. Liem
Sickle cell anemia (SCA) leads to reduced physical functioning and cardiopulmonary fitness. Prior studies suggest that airway hyperresponsiveness to bronchoprovocation testing is common in SCA, but the prevalence of exercise‐induced bronchospasm (EIB) is understudied. We hypothesized that EIB is more common in children with SCA than in controls. Non‐asthmatic subjects 10–21 years old with SCA and race‐matched controls underwent (1) maximal Cardiopulmonary Exercise Testing (CPET) by cycle ergometry and (2) a Controlled Intensity Interval Test (CIIT) consisting of eight bouts of constant workload cycling, randomized to 50% (moderate) or 70% (vigorous) of peak workload. Spirometry was performed pre/post CPET and CIIT. Multivariable logistic regression models tested associations between SCA status and EIB in response to CPET and CIIT. Compared to controls, subjects with SCA demonstrated lower hemoglobin, reduced baseline spirometry values, and decreased CPET maximal workload. Baseline lower airway obstruction and completion rates for CPET and CIIT were similar between groups. No adverse events occurred. The percentage of participants who met criteria for EIB did not differ between subjects and controls after CPET (21% vs. 26%, p = 0.537) or CIIT (32% vs. 17%, p = 0.126). In adjusted models, SCA status was not associated with EIB after CPET or CIIT. EIB was not more common in subjects with SCA versus controls after maximal CPET or submaximal exercise challenge of longer duration. Further research is needed to inform the development of exercise guidelines and to better understand the effects of exercise on airway dynamics in SCA. Trial Registration: ClinicalTrials.gov identifier: NCT03653676.
{"title":"Acute Exercise Challenge and Airway Dynamics in Youth With Sickle Cell Anemia: A Multicenter Study","authors":"Robyn T. Cohen, Jane S. Hankins, Kirsten K. Ness, Lewis L. Hsu, Tracy Baynard, Amy Tang, Shlomit Radom‐Aizik, Kevin Guerrero, Mark Rodeghier, Robert I. Liem","doi":"10.1002/ajh.70170","DOIUrl":"https://doi.org/10.1002/ajh.70170","url":null,"abstract":"Sickle cell anemia (SCA) leads to reduced physical functioning and cardiopulmonary fitness. Prior studies suggest that airway hyperresponsiveness to bronchoprovocation testing is common in SCA, but the prevalence of exercise‐induced bronchospasm (EIB) is understudied. We hypothesized that EIB is more common in children with SCA than in controls. Non‐asthmatic subjects 10–21 years old with SCA and race‐matched controls underwent (1) maximal Cardiopulmonary Exercise Testing (CPET) by cycle ergometry and (2) a Controlled Intensity Interval Test (CIIT) consisting of eight bouts of constant workload cycling, randomized to 50% (moderate) or 70% (vigorous) of peak workload. Spirometry was performed pre/post CPET and CIIT. Multivariable logistic regression models tested associations between SCA status and EIB in response to CPET and CIIT. Compared to controls, subjects with SCA demonstrated lower hemoglobin, reduced baseline spirometry values, and decreased CPET maximal workload. Baseline lower airway obstruction and completion rates for CPET and CIIT were similar between groups. No adverse events occurred. The percentage of participants who met criteria for EIB did not differ between subjects and controls after CPET (21% vs. 26%, <jats:italic>p</jats:italic> = 0.537) or CIIT (32% vs. 17%, <jats:italic>p</jats:italic> = 0.126). In adjusted models, SCA status was not associated with EIB after CPET or CIIT. EIB was not more common in subjects with SCA versus controls after maximal CPET or submaximal exercise challenge of longer duration. Further research is needed to inform the development of exercise guidelines and to better understand the effects of exercise on airway dynamics in SCA. Trial Registration: ClinicalTrials.gov identifier: NCT03653676.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"31 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796247","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}
Francesco Arcioni, Marta Bonetti, Antonella Sau, Marco Zecca, Mohsen Alzahrani, Bader Alahmari, Husam Alsadi, Ayman Almozaini, Mazen Ahmed, Mohammed Essa, Cesare Perotti, Claudia Del Fante, Cecilia Passeri, Ornella Iuliani, Anna C. Russo, Mauro Di Ianni, Mauro Marchesi, Barbara Luciani Pasqua, Marina Onorato, Laura Berchicci, Antonio Pierini, Tiziana Zei, Roberta Iacucci, Carla Cerri, Grazia Gurdo, Alessandra Innocente, Ilaria Capolsini, Paolo Gorello, Raffaella Colombatti, Raffaella Origa, Maurizio Caniglia
<p>Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a point mutation in the β-globin gene, with production of sickle hemoglobin (HbS) [<span>1, 2</span>], chronic hemolytic anemia, recurrent vaso-occlusive crises (VOCs), and progressive end-organ damage [<span>1</span>]. Although hydroxyurea and chronic transfusion therapy have improved clinical outcomes, these therapies are not curative [<span>3</span>]. Hematopoietic stem cell transplantation (HSCT) represents the only established curative approach, but its application is limited by donor availability [<span>3</span>].</p><p>Recently, gene-editing strategies, including CRISPR/Cas9 or conventional gene addition therapies, have been developed. CRISPR/Cas9 technology to disrupt the BCL11A erythroid enhancer and increase fetal hemoglobin (HbF) expression has emerged as a promising treatment [<span>4</span>]. This therapeutic approach has been validated in pivotal Phase 3 trials of exagamglogene autotemcel (exa-cel), which demonstrated near complete elimination of vaso-occlusive crises in patients with SCD and transfusion independence in most of those with β-thalassemia [<span>4, 5</span>].</p><p>However, these protocols require the collection of large numbers of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), with a minimum target of 20 × 10<sup>6</sup> CD34+ cells/kg to enable successful ex vivo manipulation and engraftment [<span>6, 7</span>]. Standard granulocyte-colony stimulating factor (G-CSF)-based mobilization is generally contraindicated due to the risk of triggering VOCs, ACS, multi-organ failure, and even death, particularly in the presence of high HbS levels [<span>8, 9</span>].</p><p>We report a case series of five patients with SCD who underwent multiple mobilization attempts in preparation for CRISPR/Cas9-based gene-editing therapy. 4/5 patients were being treated with hydroxyurea, discontinued 8 weeks before the mobilization, without reintroduction between cycles. All patients received intensive red blood cell exchange transfusion to reduce HbS to < 20% and prophylactic anticoagulation or antiplatelet therapy. Initial collection with plerixafor alone failed to achieve the CD34+ cell target in all patients. The addition of filgrastim resulted in a marked increase in CD34+ yield, without triggering VOCs or other complications. In patients who fail mobilization and manufacturing with single-agent plerixafor, no alternative mobilization strategies are available other than the combination of G-CSF and plerixafor.</p><p>Before mobilization, all patients were informed about the use of G-CSF and the associated risks (VOCs, ACS, multi-organ failure, and even death, particularly in the presence of high HbS levels). They provided both oral and written informed consent.</p><p>A 29-year-old male with compound heterozygous SCD (HbS/β<sup>+</sup> genotype) was treated at the Pediatric Oncohematology Department in Pescara and considered for CRISPR/Cas9-based
{"title":"A Combination of Plerixafor and Filgrasting Promotes Successful CD34+ Cell Collection for CRISPR/Cas9 Therapy in Sickle Cell Disease Patients With Insufficient Response to Plerixafor Alone","authors":"Francesco Arcioni, Marta Bonetti, Antonella Sau, Marco Zecca, Mohsen Alzahrani, Bader Alahmari, Husam Alsadi, Ayman Almozaini, Mazen Ahmed, Mohammed Essa, Cesare Perotti, Claudia Del Fante, Cecilia Passeri, Ornella Iuliani, Anna C. Russo, Mauro Di Ianni, Mauro Marchesi, Barbara Luciani Pasqua, Marina Onorato, Laura Berchicci, Antonio Pierini, Tiziana Zei, Roberta Iacucci, Carla Cerri, Grazia Gurdo, Alessandra Innocente, Ilaria Capolsini, Paolo Gorello, Raffaella Colombatti, Raffaella Origa, Maurizio Caniglia","doi":"10.1002/ajh.70167","DOIUrl":"10.1002/ajh.70167","url":null,"abstract":"<p>Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a point mutation in the β-globin gene, with production of sickle hemoglobin (HbS) [<span>1, 2</span>], chronic hemolytic anemia, recurrent vaso-occlusive crises (VOCs), and progressive end-organ damage [<span>1</span>]. Although hydroxyurea and chronic transfusion therapy have improved clinical outcomes, these therapies are not curative [<span>3</span>]. Hematopoietic stem cell transplantation (HSCT) represents the only established curative approach, but its application is limited by donor availability [<span>3</span>].</p><p>Recently, gene-editing strategies, including CRISPR/Cas9 or conventional gene addition therapies, have been developed. CRISPR/Cas9 technology to disrupt the BCL11A erythroid enhancer and increase fetal hemoglobin (HbF) expression has emerged as a promising treatment [<span>4</span>]. This therapeutic approach has been validated in pivotal Phase 3 trials of exagamglogene autotemcel (exa-cel), which demonstrated near complete elimination of vaso-occlusive crises in patients with SCD and transfusion independence in most of those with β-thalassemia [<span>4, 5</span>].</p><p>However, these protocols require the collection of large numbers of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), with a minimum target of 20 × 10<sup>6</sup> CD34+ cells/kg to enable successful ex vivo manipulation and engraftment [<span>6, 7</span>]. Standard granulocyte-colony stimulating factor (G-CSF)-based mobilization is generally contraindicated due to the risk of triggering VOCs, ACS, multi-organ failure, and even death, particularly in the presence of high HbS levels [<span>8, 9</span>].</p><p>We report a case series of five patients with SCD who underwent multiple mobilization attempts in preparation for CRISPR/Cas9-based gene-editing therapy. 4/5 patients were being treated with hydroxyurea, discontinued 8 weeks before the mobilization, without reintroduction between cycles. All patients received intensive red blood cell exchange transfusion to reduce HbS to < 20% and prophylactic anticoagulation or antiplatelet therapy. Initial collection with plerixafor alone failed to achieve the CD34+ cell target in all patients. The addition of filgrastim resulted in a marked increase in CD34+ yield, without triggering VOCs or other complications. In patients who fail mobilization and manufacturing with single-agent plerixafor, no alternative mobilization strategies are available other than the combination of G-CSF and plerixafor.</p><p>Before mobilization, all patients were informed about the use of G-CSF and the associated risks (VOCs, ACS, multi-organ failure, and even death, particularly in the presence of high HbS levels). They provided both oral and written informed consent.</p><p>A 29-year-old male with compound heterozygous SCD (HbS/β<sup>+</sup> genotype) was treated at the Pediatric Oncohematology Department in Pescara and considered for CRISPR/Cas9-based","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 2","pages":"394-401"},"PeriodicalIF":9.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777391","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}
Aude Mausoleo, Pascale Chretien, Astrid Laurent‐Bellue, Laurence Rocher, Lisa Fredeau, Catherine Guettier, Paul‐Albert Domnariu, Olivier Lambotte, Stephanie El Hajj, Chahinez Hani Dekimeche, Salima Hacein‐Bey‐Abina, Jean‐Charles Duclos‐Vallée, Christelle Chantalat‐Auger, Eleonora De Martin, Nicolas Noel
{"title":"Autoimmune Features in Sickle Cell Patients: A New Explanation for Liver Damage?","authors":"Aude Mausoleo, Pascale Chretien, Astrid Laurent‐Bellue, Laurence Rocher, Lisa Fredeau, Catherine Guettier, Paul‐Albert Domnariu, Olivier Lambotte, Stephanie El Hajj, Chahinez Hani Dekimeche, Salima Hacein‐Bey‐Abina, Jean‐Charles Duclos‐Vallée, Christelle Chantalat‐Auger, Eleonora De Martin, Nicolas Noel","doi":"10.1002/ajh.70168","DOIUrl":"https://doi.org/10.1002/ajh.70168","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"7 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759726","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}
Rebecca Bystrom, Laura L. Fernandes, Joseph Wynne, Dianne Pulte, Eric Hansen, Andrew J. Belli, Anna Barcellos, Christina M. Zettler, Jonathon Vallejo, Wenjuan Gu, Angelo DeClaro, Catherine C. Lerro, Ching‐Kun Wang, Donna R. Rivera, Kelly J. Norsworthy
{"title":"Real‐World Outcomes and Treatment Patterns in Patients With Acute Myeloid Leukemia and TP53 Gene Mutation or 17p Deletion","authors":"Rebecca Bystrom, Laura L. Fernandes, Joseph Wynne, Dianne Pulte, Eric Hansen, Andrew J. Belli, Anna Barcellos, Christina M. Zettler, Jonathon Vallejo, Wenjuan Gu, Angelo DeClaro, Catherine C. Lerro, Ching‐Kun Wang, Donna R. Rivera, Kelly J. Norsworthy","doi":"10.1002/ajh.70165","DOIUrl":"https://doi.org/10.1002/ajh.70165","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"11 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731047","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}
Zishi Fang, Jie Yu, Wei Liu, Ang Wei, Qing Zhang, Jianpei Fang, Shaoyan Hu, Xiaoyan Wu, Jian Wang, Weihong Zhao, Aiguo Liu, Shilin Liu, Xuerong Li, Yongjun Fang, Jingshi Wang, Yuan Sun, Rong Liu, Leping Zhang, Yongmin Tang, Dongsheng Huang, Xiaojun Yuan, Liming Sun, Jian Ge, Yunze Zhao, Dong Wang, Wenqian Wang, Chenxin Zhou, Zhigang Li, Tianyou Wang, Rui Zhang, for the Chinese Children's Histiocyte Group
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The widely used HLH-1994/2004 protocols are primarily designed for primary HLH (pHLH). However, in Asia, particularly in China, secondary HLH (sHLH) is more prevalent, which may limit the efficacy of these protocols and increase treatment-related toxicity. To address this, we conducted a multicenter, prospective, single-arm clinical study to evaluate the CCHG-HLH-2018 protocol, a stratified treatment regimen based on glucocorticoids and etoposide, for pediatric HLH patients in China. A total of 286 patients from 20 centers were included, with a median follow-up of 64 months. Based on HLH-related indicators at onset, 64 patients (22.4%) were classified as low-risk group and 222 (77.6%) as high-risk group. The 5-year overall survival (OS) for all patients was 86.3% (95% CI, 81.7–89.8), with 96.9% (95% CI, 88.1–99.2) in low-risk group and 83.2% (95% CI, 77.6–87.5) in high-risk group (Holm-Bonferroni adjusted p = 0.006). The 5-year OS for pHLH patients was 72.9% (95% CI, 58.0–83.3), significantly lower than the 89.0% (95% CI, 84.3–92.4) for sHLH patients (Holm-Bonferroni adjusted p = 0.008). Among all patients, 54 (18.9%) achieved sustained remission without chemotherapy. No significant differences in OS and EFS were observed between high-risk patients receiving CSA-containing regimens and those receiving non-CSA regimens (p = 0.148, p = 0.107). However, exploratory subgroup analysis of idiopathic HLH patients suggested a trend toward improved survival with the CSA-containing regimen. The safety profile of the CCHG-HLH-2018 protocol was acceptable, with fewer adverse events in the low-risk group. Our findings suggest this stratified protocol is effective in reducing chemotherapy intensity for Chinese children with HLH.
{"title":"Long-Term Outcomes of a Stratified Treatment Regimen Based on Etoposide and Glucocorticoids in Children With Hemophagocytic Lymphohistiocytosis (CCHG-HLH-2018): A Multicenter, Single-Arm Clinical Study","authors":"Zishi Fang, Jie Yu, Wei Liu, Ang Wei, Qing Zhang, Jianpei Fang, Shaoyan Hu, Xiaoyan Wu, Jian Wang, Weihong Zhao, Aiguo Liu, Shilin Liu, Xuerong Li, Yongjun Fang, Jingshi Wang, Yuan Sun, Rong Liu, Leping Zhang, Yongmin Tang, Dongsheng Huang, Xiaojun Yuan, Liming Sun, Jian Ge, Yunze Zhao, Dong Wang, Wenqian Wang, Chenxin Zhou, Zhigang Li, Tianyou Wang, Rui Zhang, for the Chinese Children's Histiocyte Group","doi":"10.1002/ajh.70158","DOIUrl":"10.1002/ajh.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The widely used HLH-1994/2004 protocols are primarily designed for primary HLH (pHLH). However, in Asia, particularly in China, secondary HLH (sHLH) is more prevalent, which may limit the efficacy of these protocols and increase treatment-related toxicity. To address this, we conducted a multicenter, prospective, single-arm clinical study to evaluate the CCHG-HLH-2018 protocol, a stratified treatment regimen based on glucocorticoids and etoposide, for pediatric HLH patients in China. A total of 286 patients from 20 centers were included, with a median follow-up of 64 months. Based on HLH-related indicators at onset, 64 patients (22.4%) were classified as low-risk group and 222 (77.6%) as high-risk group. The 5-year overall survival (OS) for all patients was 86.3% (95% CI, 81.7–89.8), with 96.9% (95% CI, 88.1–99.2) in low-risk group and 83.2% (95% CI, 77.6–87.5) in high-risk group (Holm-Bonferroni adjusted <i>p</i> = 0.006). The 5-year OS for pHLH patients was 72.9% (95% CI, 58.0–83.3), significantly lower than the 89.0% (95% CI, 84.3–92.4) for sHLH patients (Holm-Bonferroni adjusted <i>p</i> = 0.008). Among all patients, 54 (18.9%) achieved sustained remission without chemotherapy. No significant differences in OS and EFS were observed between high-risk patients receiving CSA-containing regimens and those receiving non-CSA regimens (<i>p</i> = 0.148, <i>p</i> = 0.107). However, exploratory subgroup analysis of idiopathic HLH patients suggested a trend toward improved survival with the CSA-containing regimen. The safety profile of the CCHG-HLH-2018 protocol was acceptable, with fewer adverse events in the low-risk group. Our findings suggest this stratified protocol is effective in reducing chemotherapy intensity for Chinese children with HLH.</p>\u0000 <p><b>Trial Registration:</b> http://www.chictr.org.cn, identifier: ChiCTR1800017267</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 2","pages":"291-303"},"PeriodicalIF":9.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732712","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}
Tiziano Barbui,Arianna Ghirardi,Valerio De Stefano
{"title":"Extending the Biological Axis Linking CHIP to Cancer Emergence.","authors":"Tiziano Barbui,Arianna Ghirardi,Valerio De Stefano","doi":"10.1002/ajh.70162","DOIUrl":"https://doi.org/10.1002/ajh.70162","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"18 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710828","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}
Alexander Röth, Wilma Barcellini, Christine Ademokun, Junho Jang, Maria Luisa Lozano, David Valcarcel Ferreiras, Cristina Pascual-Izquierdo, Shripad Chitnis, Sofiya Matviykiv, Alessandra Vitaliti, Chi Chen, Vasiliki Katsanou, Raghav Chawla, Hanny Al-Samkari
Iptacopan is a first-in-class, oral, selective inhibitor of complement factor B that has demonstrated positive efficacy across several complement-driven diseases. Here we evaluate the efficacy and safety of iptacopan monotherapy in adult patients with primary immune thrombocytopenia (ITP) and primary cold agglutinin disease (CAD). We performed a global, multicenter, phase 2 basket study enrolling patients with primary ITP or CAD after failure of ≥ 1 unique prior therapies. Primary endpoints were platelet response (≥ 50 × 109/L) for ITP and hemoglobin response (≥ 1.5 g/dL increase) for CAD sustained for ≥ 2 consecutive weeks during the first 12 weeks of iptacopan treatment, without the use of rescue therapy. Other endpoints included time to first response, duration of response, pharmacokinetics, safety/tolerability, and FACIT-Fatigue. Nineteen patients were treated with iptacopan (9 ITP, 10 CAD). Among patients with CAD, most showed improvements in hemoglobin levels, with a mean increase of 2.2 g/dL from baseline to week 12; five (50%) patients achieved the primary endpoint. Improvements were also observed for other outcomes in CAD, including lactate dehydrogenase, bilirubin, reticulocytes, and FACIT-Fatigue. Conversely, no patients with ITP met the primary endpoint. Most treatment-emergent adverse events (TEAEs) were mild, the most common being headache (21%), asthenia (16%), fatigue (16%), and petechiae (16%). Iptacopan monotherapy demonstrated encouraging preliminary efficacy in primary CAD, while no protocol-defined responses were observed in primary ITP. Iptacopan may represent a promising oral option for CAD and was well tolerated in both ITP and CAD with no unexpected safety signals.
{"title":"Iptacopan for Immune Thrombocytopenia and Cold Agglutinin Disease: A Global Phase 2 Basket Clinical Trial","authors":"Alexander Röth, Wilma Barcellini, Christine Ademokun, Junho Jang, Maria Luisa Lozano, David Valcarcel Ferreiras, Cristina Pascual-Izquierdo, Shripad Chitnis, Sofiya Matviykiv, Alessandra Vitaliti, Chi Chen, Vasiliki Katsanou, Raghav Chawla, Hanny Al-Samkari","doi":"10.1002/ajh.70147","DOIUrl":"10.1002/ajh.70147","url":null,"abstract":"<p>Iptacopan is a first-in-class, oral, selective inhibitor of complement factor B that has demonstrated positive efficacy across several complement-driven diseases. Here we evaluate the efficacy and safety of iptacopan monotherapy in adult patients with primary immune thrombocytopenia (ITP) and primary cold agglutinin disease (CAD). We performed a global, multicenter, phase 2 basket study enrolling patients with primary ITP or CAD after failure of ≥ 1 unique prior therapies. Primary endpoints were platelet response (≥ 50 × 10<sup>9</sup>/L) for ITP and hemoglobin response (≥ 1.5 g/dL increase) for CAD sustained for ≥ 2 consecutive weeks during the first 12 weeks of iptacopan treatment, without the use of rescue therapy. Other endpoints included time to first response, duration of response, pharmacokinetics, safety/tolerability, and FACIT-Fatigue. Nineteen patients were treated with iptacopan (9 ITP, 10 CAD). Among patients with CAD, most showed improvements in hemoglobin levels, with a mean increase of 2.2 g/dL from baseline to week 12; five (50%) patients achieved the primary endpoint. Improvements were also observed for other outcomes in CAD, including lactate dehydrogenase, bilirubin, reticulocytes, and FACIT-Fatigue. Conversely, no patients with ITP met the primary endpoint. Most treatment-emergent adverse events (TEAEs) were mild, the most common being headache (21%), asthenia (16%), fatigue (16%), and petechiae (16%). Iptacopan monotherapy demonstrated encouraging preliminary efficacy in primary CAD, while no protocol-defined responses were observed in primary ITP. Iptacopan may represent a promising oral option for CAD and was well tolerated in both ITP and CAD with no unexpected safety signals.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT05086744</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 2","pages":"242-254"},"PeriodicalIF":9.9,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710829","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：