0
selected
-
1.
The Role of Iron in Benign and Malignant Hematopoiesis.
Sinha, S, Pereira-Reis, J, Guerra, A, Rivella, S, Duarte, D
Antioxidants & redox signaling. 2021;(6):415-432
-
-
Free full text
-
Abstract
Significance: Iron is an essential element required for sustaining a normal healthy life. However, an excess amount of iron in the bloodstream and tissue generates toxic hydroxyl radicals through Fenton reactions. Henceforth, a balance in iron concentration is extremely important to maintain cellular homeostasis in both normal hematopoiesis and erythropoiesis. Iron deficiency or iron overload can impact hematopoiesis and is associated with many hematological diseases. Recent Advances: The mechanisms of action of key iron regulators such as erythroferrone and the discovery of new drugs, such as ACE-536/luspatercept, are of potential interest to treat hematological disorders, such as β-thalassemia. New therapies targeting inflammation-induced ineffective erythropoiesis are also in progress. Furthermore, emerging evidences support differential interactions between iron and its cellular antioxidant responses of hematopoietic and neighboring stromal cells. Both iron and its systemic regulator, such as hepcidin, play a significant role in regulating erythropoiesis. Critical Issues: Significant pre-clinical studies are on the way and new drugs targeting iron metabolism have been recently approved or are undergoing clinical trials to treat pathological conditions with impaired erythropoiesis such as myelodysplastic syndromes or β-thalassemia. Future Directions: Future studies should explore how iron regulates hematopoiesis in both benign and malignant conditions. Antioxid. Redox Signal. 35, 415-432.
-
2.
Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy.
Kichula, EA, Proud, CM, Farrar, MA, Kwon, JM, Saito, K, Desguerre, I, McMillan, HJ
Muscle & nerve. 2021;(4):413-427
-
-
Free full text
-
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive, neurodegenerative disease caused by biallelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is characterized by motor neuron degeneration, resulting in progressive muscle atrophy and weakness. Before the emergence of disease-modifying therapies, children with the most severe form of SMA would never achieve the ability to sit independently. Only 8% survived beyond 20 months of age without permanent ventilator support. One such therapy, onasemnogene abeparvovec, an adeno-associated virus-based gene replacement therapy, delivers functional human SMN through a one-time intravenous infusion. In addition to substantially improving survival, onasemnogene abeparvovec was found to increase motor milestone attainment and reduce the need for respiratory or nutritional support in many patients. This expert opinion provides recommendations and practical considerations on the patient-centered decisions to use onasemnogene abeparvovec. Recommendations include the need for patient-centered multidisciplinary care and patient selection to identify those with underlying medical conditions or active infections to reduce risks. We also describe the importance of retesting patients with elevated anti-adeno-associated virus serotype 9 antibodies. Recommendations for prednisolone tapering and monitoring for potential adverse events, including hepatotoxicity and thrombotic microangiopathy, are described. The need for caregiver education on managing day-to-day care at time of treatment and patient- and family-centered discussions on realistic expectations are also recommended. We detail the importance of following standard-of-care guidance and long-term monitoring of all children with SMA who have received one or more disease-modifying therapy using registries. We also highlight the need for presymptomatic or early symptomatic treatment of this disorder.
-
3.
Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept.
González Astorga, B, Salvà Ballabrera, F, Aranda Aguilar, E, Élez Fernández, E, García-Alfonso, P, González Flores, E, Vera García, R, Fernández Montes, A, López Muñoz, AM, Salud Salvia, A
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2021;(8):1520-1528
-
-
Free full text
-
Abstract
Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient's profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.
-
4.
Telitacicept: First Approval.
Dhillon, S
Drugs. 2021;(14):1671-1675
Abstract
Telitacicept (Tai'ai®) is fusion protein comprising a recombinant transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor fused to the fragment crystallizable (Fc) domain of human immunoglobulin G (IgG). Telitacicept is being developed by Yantai Rongchang Pharmaceutical through its subsidiary RemeGen for the treatment of B cell-mediated autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS). Telitacicept binds to and neutralizes the activity of two cell-signalling molecules, B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby suppressing the development and survival of plasma cells and mature B cells. In March 2021, telitacicept received its first approval in China for the treatment of patients with active SLE. Clinical studies of telitacicept in several other indications, including IgA nephropathy, MS, myasthenia gravis, neuromyelitis optica spectrum disorders, RA and Sjögren's syndrome are underway in China. This article summarizes the milestones in the development of telitacicept leading to this first approval for SLE.
-
5.
Updates on the Management of Ocular Vasculopathies with VEGF Inhibitor Conbercept.
Liu, H, Ma, Y, Xu, HC, Huang, LY, Zhai, LY, Zhang, XR
Current eye research. 2020;(12):1467-1476
Abstract
Purpose: To provide a detailed review on the therapeutic efficacy of conbercept for the management of ocular vasculopathies. Methods: A comprehensive literature search of various electronic databases was performed. Results: Ocular vasculopathy is one of the major causes of visual impairment and blindness which includes a range of disorders. Vascular endothelial growth factor (VEGF) regulates angiogenesis, enhances vascular permeability, and drives the formation of neovascularization. Anti-VEGF therapy has been shown to prevent vision loss or potentially improve vision in patients with exudative or neovascular retinal disease. The most recent anti-VEGF drug in China is conbercept. In the USA and Europe, bevacizumab is the most recently approved anti-VEGF agent. Conclusions: Conbercept serves as another anti-VEGF option for patients with neovascular AMD and other retinal vascular disorders. There have not been many clinical trials that study conbercept as compared with other currently available anti-VEGF drugs. There is a need for large-scale, well-designed, randomized clinical trials to ensure its long-term safety and efficacy and to determine if it has any advantages over other anti-VEGF agents.
-
6.
How we manage adults with myelodysplastic syndrome.
Fenaux, P, Platzbecker, U, Ades, L
British journal of haematology. 2020;(6):1016-1027
-
-
Free full text
-
Abstract
The prognosis in Myelodysplastic syndromes (MDS), although recently refined by molecular studies, remains largely based on conventional prognostic scores [International Prognostic Scoring System (IPSS), revised IPSS], classifying patients into "lower risk" MDS (LR-MDS) and "higher risk" MDS (HR-MDS). In LR-MDS, treatment mainly aims at improving cytopenias, principally anaemia, while in HR-MDS it aims at delaying disease progression and prolonging survival. In LR-MDS without deletion 5q, anaemia is generally treated first by erythropoietic stimulating factors, while second line treatments are currently not approved [lenalidomide, hypomethylating agents (HMA), luspatercept] or rarely indicated (antithymocyte globulin). Lenalidomide has major efficacy in LR-MDS with deletion 5q. Allogeneic stem cell transplantation (allo-SCT) is sometimes considered in LR-MDS, and iron chelation can be considered when multiple red blood cell transfusions are required. Allo-SCT is the only potentially curative treatment for HR-MDS; however, it is rarely applicable. It is generally preceded by intensive chemotherapy (IC) or HMA in patients with excess of marrow blasts (especially if >10%). In other patients, HMA can improve survival. The role of new drugs, including venetoclax or, in case of specific mutations, IDH1 or IDH2 inhibitors, is investigated. IC is mainly indicated as a bridge to allo-SCT, in the absence of unfavourable karyotype.
-
7.
A promising outlook for diabetic kidney disease.
Cooper, M, Warren, AM
Nature reviews. Nephrology. 2019;(2):68-70
-
8.
Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis.
Fenaux, P, Kiladjian, JJ, Platzbecker, U
Blood. 2019;(8):790-794
-
-
Free full text
-
Abstract
Anemia of lower-risk myelodysplastic syndromes (MDSs) and primary myelofibrosis (PMF) generally becomes resistant to available treatments, leading to red blood cell (RBC) transfusions, iron overload, shortened survival, and poor quality of life. The transforming growth factor-β superfamily, including activins and growth differentiation factors (GDFs), is aberrantly expressed in lower-risk MDSs and PMF. Luspatercept (and sotatercept), ligand traps that particularly inhibit GDF11, lead to RBC transfusion independence in 10% to 50% of lower-risk MDSs resistant to available treatments, and have started to be used in PMF.
-
9.
Novel therapies in low- and high-risk myelodysplastic syndrome.
Germing, U, Schroeder, T, Kaivers, J, Kündgen, A, Kobbe, G, Gattermann, N
Expert review of hematology. 2019;(10):893-908
Abstract
Introduction: Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms with diverse clinical courses. The revised version of the international prognostic scoring system (IPSS-R) provides risk stratification into 5 different groups. Areas covered: For lower-risk patients, red blood cell transfusions and iron chelation are the backbone of supportive care. In addition, erythropoiesis-stimulating agents (ESA) are used to ameliorate anemia. Lenalidomide is approved for the treatment of lower-risk patients with del(5q) who are transfusion-dependent. Patients with higher-risk disease should be offered allogeneic stem cell transplantation whenever possible. If they are unfit for transplantation or an appropriate donor cannot be found, hypomethylating agents may be used. Expert opinion: New therapeutic options for lower-risk patients include thrombopoietin analogues, the TGF-beta family ligand trapping drug Luspatercept, and the telomerase inhibitor Imetelstat. Combinations of hypomethylating agents (HMA) with other compounds, and inhibitors of bcl2, such as venetoclax are being developed for higher-risk patients. Finally, hypomethylating agents in combination with donor lymphocytes may lead to long-term remission following molecular or hematological relapse after allogeneic SCT.
-
10.
Intravitreal Aflibercept in Diabetic Macular Edema: Long-Term Outcomes.
Introini, U, Casalino, G
Developments in ophthalmology. 2017;:71-77
Abstract
For decades, macular laser photocoagulation has been the standard of care in the treatment of diabetic macular edema (DME). With the relatively recent advent of anti-vascular endothelial growth factor (VEGF) agents, DME treatment has entered a new era. VEGF is a well-known pro-angiogenic and pro-permeability factor involved in the pathogenesis of DME. VEGF blockade has proven remarkably effective at reducing DME and improving visual acuity (VA) in eyes with center involved DME causing VA loss in several randomized controlled trials (RCTs). Intravitreal aflibercept, ranibizumab, and bevacizumab (the latter used off-label) are 3 anti-VEGF molecules currently available for DME treatment. Aflibercerpt is a 115-kDA recombinant fusion protein consisting of VEGF binding domains of human VEGF receptors-1 and -2 fused to the Fc domain of human immunoglobulin-G1. The ability to bind placental growth factors 1 and 2 (which is another pro-permeability mediator) and a theoretically long half-life are potential advantages of aflibercept over other anti-VEGF agents. The use of intravitreal aflibercept in DME treatment has been investigated in several RCTs. The aim of this chapter is to briefly report on the current evidence for treating DME with intravitreal aflibercept.