Iptacopan for Immune Thrombocytopenia and Cold Agglutinin Disease: A Global Phase 2 Basket Clinical Trial

ABSTRACT 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 9 /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. Trial Registration: ClinicalTrials.gov identifier: NCT05086744

Albuminuria Predicts a Rapid Decline in Kidney Function in 2 International, Longitudinal Cohorts of Adults With Sickle Cell Anemia

ABSTRACT Chronic kidney disease (CKD) is common and a major contributor to increased morbidity and early mortality in people with sickle cell anemia (SCA). Urine albumin‐to‐creatinine ratio (uACR) is recommended to identify patients with SCA‐related CKD but its utility in predicting long‐term kidney dysfunction remains unclear in this patient population. In two independent, longitudinal cohorts of patients with hemoglobin SS or Sβ 0 ‐thalassemia (USA: n  = 268, median follow‐up 6 years; France: n  = 310, median follow‐up 8.2 years) we investigated the utility of uACR, as well as other clinical and modifiable risk factors, for predicting a decline in kidney function as determined by the rate of estimated glomerular filtration rate (eGFR) decline. Using linear mixed‐effects models, a higher baseline uACR independently predicted a faster rate of eGFR decline as well as a more rapid annual eGFR decline, defined as ≥ 3 mL/min/1.73m 2 ( p  ≤ 0.009). Furthermore, baseline uACR of ≥ 100 mg/g creatinine was independently associated with the rate of eGFR decline and rapid annual eGFR decline in both cohorts. Tobacco smoking was also associated with a faster rate of eGFR decline and was congruous between the two cohorts. In conclusion, we demonstrate that uACR is an important clinical tool that predicts a more rapid decline in kidney function and should be routinely monitored in people with SCA. Our data also support preventative care to reduce tobacco smoking for mitigating the risk of CKD progression in this high‐risk population.

Beyond the Usual Suspects: RSV Infection in Patients With Hematological Malignancies Compared to Influenza and SARS‐COV‐2—A Report From the EPICOVIDEHA/EPIRESEHA Registry

Adult‐Onset β‐Thalassemia Major as Acquired Imprinting Disorder

Iron Overload and Anemia in Transferrin Immune Complex Disease, an Overlooked Monoclonal Gammopathy of Clinical Significance

Chimeric Antigen Receptor T‐Cells ( CAR T‐Cells) in Hematological Malignancies: A Systematic Review and Meta‐Analysis of Proportions From Clinical Trials

ABSTRACT This meta‐analysis examined the safety and efficacy of CAR T‐cell therapy in 3281 patients with hematological malignancies enrolled in phase 1/2, 2 and 3 clinical trials, published until July 23, 2025 according to the PRISMA guidelines. All trials involved relapsed/refractory, pretreated individuals. In 11 multiple myeloma trials, CAR T‐cell therapy showed significant efficacy, with pooled ORR and ≥CR rates of 89% and 53%, respectively. These responses translated into important survival benefits, with 1‐year OS and PFS rates of 84% and 60%, respectively. However, AEs including any‐grade CRS, infections and grade ≥ 3 neutropenia emerged in pooled rates of 89%, 46% and 88%, respectively. In 23 trials on high‐grade lymphomas, the pooled ORR was 76% and the pooled ≥CR rate 55%. The pooled 1‐year OS and PFS rates were 65% and 46%, respectively. Any‐grade CRS was prevalent in a pooled rate of 46% and grade ≥ 3 neutropenia in 56%. Data from 16 records investigating CAR T‐cells for leukemia yielded pooled ORR and ≥CR rates of 78% and 70%, respectively, with pooled 1‐year OS and PFS rates being 61% and 40%, respectively. Similarly to myeloma and lymphoma, any‐grade CRS was very common at a pooled rate of 85% and any‐grade infections occurred at a pooled rate of 29%. Apart from grade ≥ 3 neutropenia (70%), grade ≥ 3 anemia emerged as an equally common serious hematological AE (69%). In conclusion, CAR T‐cells constitute a highly effective therapeutic option for patients with hematological cancer at relapse, but close patient monitoring is essential to address treatment‐related toxicities.

Associations Between Sex, Disease Features and Outcome in Patients With Acute Myeloid Leukemia: A Sex‐Stratified Analysis of the GIMEMA AML1310 Trial

Complement Biomarkers for Monitoring Last‐Generation Complement Inhibitors in Paroxysmal Nocturnal Hemoglobinuria Patients

A Rare Combination of High‐Affinity Hemoglobin, Non‐Transfusion‐Dependent Thalassemia (Αlpha‐Triplication and Codon 39 Mutation), and Hereditary Stomatocytosis

Tolerability and Outcomes With Serial Cycles of 28 Days of Venetoclax in Newly Diagnosed Patients With Acute Myeloid Leukemia

ABSTRACT The standard of care for newly‐diagnosed unfit patients with acute myeloid leukemia (AML) is venetoclax (VEN) with azacitidine (AZA). In the phase 3 trial, before remission, AZA was given with 28 days of VEN. This regimen is myelosuppressive; therefore, many decrease VEN duration before and/or after initial response assessment. We report our center's outcomes administering 28 days of VEN preremission, and in most cases, postremission, relying on other strategies to reduce cytopenias. All newly‐diagnosed patients with AML treated outside of a clinical trial with VEN/AZA for > 7 days at our center from 2018 to 2024 were reviewed. 134 patients met inclusion criteria; median age was 70 years (interquartile range [IQR] 64–76), 57% male, and 63% had European LeukemiaNet adverse risk AML (85/134). Overall response rate (including complete remission and complete remission with incomplete hematologic recovery) was 87/134 (64.9%). Median cycles completed was 2 (IQR 1–3, range 0–26), with 117 (87%) completing ≥ 1 cycle with a response assessment. Median duration of cycles 1–5 was 42 days. Median overall survival was 381 days. Prior to response assessment, 113/117 (96.6%) received 28 days of VEN. Postresponse, 17/81 (21.0%) had a VEN reduction (in duration or dose). Grade ≥ 3 neutropenia or thrombocytopenia was higher in cycle 1 than in similar studies, without differences in transfusion needs or infectious complications. Hematologic toxicities improved with subsequent cycles. Serial cycles with 28 days of VEN can be administered pre‐ and postremission with higher early myelosuppression but similar transfusion and infection rates compared to studies of reduced VEN duration.