Publications by authors named "J-J Kiladjian"
Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 10/L. Whether this association occurs in patients with thrombocytopenia is unclear.
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- The ACE-536-MF-001 trial studied the effects of luspatercept on myelofibrosis patients, enrolling 95 participants divided into four groups based on their dependency on transfusions and anemia status.
- The primary outcome measured was the anemia response rate, where 14%-26% of patients met the criteria based on their cohort, with significant hemoglobin increases noted, particularly in non-transfusion dependent patients.
- Adverse events were common, with 94% of patients experiencing at least one; the most frequent were hypertension and other manageable issues, while the treatment showed consistent efficacy and safety results similar to previous studies.
Article Synopsis
- - The phase 3 PERSIST-2 study showed that the JAK2/IRAK1 inhibitor pacritinib improved anemia in patients with cytopenic myelofibrosis.
- - Pacritinib was found to inhibit the ACVR1 receptor more effectively than other similar drugs, which is believed to lower hepcidin production and improve anemia.
- - Among patients who were not transfusion independent at the start of the study, a much higher percentage achieved transfusion independence with pacritinib compared to those receiving the best available therapy.
Article Synopsis
- Janus kinase inhibitors (JAKis) like ruxolitinib are standard treatments for symptomatic myelofibrosis but can lead to treatment discontinuation due to disease progression and side effects.
- * The combination of JAKis with BET inhibitors, such as pelabresib, has shown promise in clinical trials, improving spleen volume and total symptom scores in patients with myelofibrosis.
- * An analysis comparing this combination therapy to standard JAKi monotherapy suggests that pelabresib with ruxolitinib may be more effective in treating treatment-naive patients with myelofibrosis.
Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib).
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- Momelotinib is the first inhibitor targeting both JAK1, JAK2, and ACVR1, showing benefits in treating symptoms of myelofibrosis (MF), like splenomegaly and anemia.
- A long-term analysis pooled data from three phase 3 studies involving 725 MF patients, with some remaining on momelotinib for over 5 years.
- The treatment had a manageable safety profile, with diarrhea as the most common side effect, and no increase in serious adverse events over time.
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic complement-mediated hemolysis. C5 inhibition controls intravascular hemolysis in untreated PNH but cannot address extravascular hemolysis. Pegcetacoplan, a pegylated peptide targeting proximal complement protein C3, potentially inhibits both intravascular and extravascular hemolysis.
View Article and Find Full Text PDFPAC203 is a randomized dose-finding study of pacritinib, an oral JAK2/IRAK1 inhibitor, in patients with advanced myelofibrosis who are intolerant of or resistant to ruxolitinib. Patients were randomized 1:1:1 to pacritinib 100 mg once per day, 100 mg twice per day, or 200 mg twice per day. Enhanced eligibility criteria, monitoring, and dose modifications were implemented to mitigate risk of cardiac and hemorrhagic events.
View Article and Find Full Text PDFActivation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity.
View Article and Find Full Text PDFBackground: Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea.
Methods: We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients).