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Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients. METHODS In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. RESULTS In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusions; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients received no transfusion; none of the patients in the second trial received transfusions. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan. CONCLUSIONS Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia -- in whom iptacopan showed superiority to anti-C5 therapy -- and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.) [ABSTRACT FROM AUTHOR]

This article presents the results of group discussion among an ad hoc constituted panel of experts aimed at identifying and addressing unmet clinical needs (UCNs) in the management of infectious risk associated with eculizumab or new terminal complement inhibitors (CIs) in paroxysmal nocturnal hemoglobinuria (PNH). With the Delphi technique, the most clinically relevant UCNs in PNH patients candidate to or on terminal CI were selected. They resulted to be: optimizing the infection prevention measures; developing non pharmacological infectious risk-mitigation strategies; improving the management of disease exacerbation during infectious complications. For each of these issues consensus opinions were provided and, when appropriate, proposals for advancement in clinical practice were addressed. The hope is that this comprehensive overview will serve to improve the practice of CIs therapy and inform the design and implementation of new studies in the field., Competing Interests: Declaration of Competing Interest C. Girmenia has received honoraria from Gilead Sciences, MSD, Pfizer Pharmaceuticals, Celgene, Novartis, Janssen, Takeda, Amgen, GSK, Biotest and Alexion Pharmaceuticals. W. Barcellini has received honoraria from Agios, Alexion, Apellis, Biocryst, Incyte, Janssen, Momenta, Novartis, Sanofi, SOBI and Alexion Pharmaceuticals. P. Bianchi has received honoraria from Agios Pharmaceuticals, Rocket Pharmaceuticals and Alexion Pharmaceuticals. E. Di Bona has received honoraria from Alexion Pharmaceuticals a. A.P. Iori has received honoraria from Novartis, Takeda, Amgen, JAZZ and Alexion Pharmaceuticals. R. Notaro has received honoraria from BioCryst, SOBI Pharmaceuticals and Alexion Pharmaceuticals. S. Sica: has received honoraria from Amgen Jazz, Pfizer, Astellas, Sobi and Alexion Pharmaceuticals. A. Zanella has received honoraria from Agios e Rocket Pharma. and Alexion Pharmaceuticals. A. De Vivo has received honoraria from Takeda Italia, Sobi Italia and Alexion Pharmaceuticals. G.Barosi has received honoraria from Alexion Pharmaceuticals. A. Risitano has received honoraria from Apellis, Sobi, Novartis, Roche, Samsung, Pfizer and Alexion Pharmaceuticals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The addition of venetoclax to hypomethylating agents (HMA-V) improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive treatment. The aim of our study was to confirm data reported in literature, in a real-life multicenter experience. We retrospectively evaluated 56 naïve AML patients who received HMA-V at 8 different collaborating Hematology Units in the North-East of Italy, from September 2018 to October 2020. Patients received azacitidine or decitabine at standard dose, adding venetoclax starting from cycle 1-3. The median time-to-response was 2 cycles and composite complete remission rate (CCR) was 67.9%. Thirteen out of 38 responders (34.2%) relapsed, with a median response duration of 13.7 months. Transfusion independence (TI) was obtained in 27 (87.0%) and 28 (90.3%) out of 31 patients for red blood cells and platelets, respectively. Median OS was 12.3 months (95% CI, 8.1-16.5), and median PFS was 11.3 months (95% CI, 4.6-17.9). Cytogenetic risk was the only variable impacting on survival, while no differences were observed stratifying patients by age, bone marrow blasts, WHO classification or type of HMA. In conclusion, our real-life multicenter experience indicates that HMA-V treatment allows achieving good response rates in naïve AML patients, ineligible for intensive chemotherapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)