Latest news with #azacitidine
Medscape
31-07-2025
- Health
- Medscape
Novel Combo Boosts Survival in IDH1-Mutated AML
TOPLINE: Ivosidenib combined with azacitidine extended median overall survival to 29.3 months compared with 7.9 months for placebo plus azacitidine in newly diagnosed isocitrate dehydrogenase 1 (IDH1)-mutated acute myeloid leukemia (AML). The combination therapy also improved hematologic recovery and increased transfusion independence rate to 53.8% vs 17.1% with placebo. METHODOLOGY: A total of 148 patients with newly diagnosed IDH1-mutated AML who were unfit for intensive chemotherapy were randomized to receive either ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75). Treatment consisted of 500 mg ivosidenib or placebo administered orally once daily, combined with subcutaneous or intravenous 75 mg/m² azacitidine for 7 days in 28-day cycles, with randomization stratified by geographic region and disease status. Analysis included a median follow-up period of 28.6 months, with overall survival as the key outcome measure, along with hematologic recovery, transfusion independence, and molecular measurable residual disease response. TAKEAWAY: Median overall survival was significantly longer with ivosidenib-azacitidine at 29.3 months (95% CI, 13.2-not reached) compared to 7.9 months (95% CI, 4.1-11.3) with placebo-azacitidine (hazard ratio [HR], 0.42; 95% CI, 0.27-0.65; P < .0001). Among patients who were transfusion dependent at baseline, conversion to transfusion independence was achieved in 53.8% (21/39) of ivosidenib-azacitidine patients vs 17.1% (7/41) of placebo-azacitidine patients (P = .0004). Of 33 ivosidenib-treated patients evaluable for molecular measurable residual disease, 10 (30.3%) achieved MRD negativity by day 1 of cycle 14, all of whom had complete remission. The safety profile remained consistent with previous reports, with lower rates of febrile neutropenia and infections in the ivosidenib-azacitidine arm, though neutropenia and bleeding events were more common than with placebo. IN PRACTICE: 'These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy-ineligible patients with IDH1-mutated AML,' the authors of the study wrote. SOURCE: The study was led by Pau Montesinos, Hospital Universitari i Politécnic La Fe in Valencia, Spain, and Hartmut Döhner, Ulm University Hospital in Ulm, Germany. It was published online in Blood Advances. LIMITATIONS: According to the authors, molecular response analysis was limited by the small number of measurable residual disease-evaluable patients and samples, as well as the discontinuation of sample collection after study unblinding in March 2021. The limited number of variants that could be tracked with sufficient sensitivity in panel-based next-generation sequencing measurable residual disease assessment also constrained the molecular analyses. DISCLOSURES: Montesinos disclosed having relationships with AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer, Sanofi, Servier, and Teva Pharmaceuticals. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
19-06-2025
- Health
- Medscape
Azacitidine Shows Promise in Treating VEXAS Syndrome
Azacitidine showed potential in treating patients with VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, offering high response rates and reducing the use of glucocorticoids. Tocilizumab and anakinra also demonstrated effectiveness, with a higher discontinuation rate seen with the latter. METHODOLOGY: Researchers conducted a retrospective cohort study in the UK and analyzed 71 treatment courses in 59 patients with genetically confirmed VEXAS syndrome (mean age at treatment initiation, 71 years; 98% men) across six major tertiary referral centers from July 2014 to October 2024. Patients received five categories of targeted therapy: Tocilizumab (n = 19), anakinra (n = 13), azacitidine (n = 13), baricitinib (n = 11), and prednisolone alone (n = 10). Data were collected at diagnosis, treatment initiation, and follow-ups at 3 months, 6 months, and 12 months. Primary outcomes were complete response (defined as clinical remission with a C-reactive protein level ≤ 10 mg/L and requirement of ≤ 10 mg/d prednisolone) and partial response (defined as clinical remission with at least a 50% reduction in both C-reactive protein level and glucocorticoid dose from baseline). Adverse events and treatment discontinuation were documented, with serious events defined as those requiring permanent discontinuation. The study followed methods used in a French cohort study with adjustments to only the statistical reporting format to enable comparisons. TAKEAWAY: Azacitidine showed a 91% overall response rate at 6 months (10 of 11 patients), with 27% of patients achieving complete response, and maintained effectiveness at 12 months. Glucocorticoid-sparing effects were notable with prednisolone doses reduced to ≤ 5 mg/d in 60% of patients on azacitidine at 12 months. Anakinra showed promising initial responses at 3 months (seven of eight patients), with a 100% response rate at 6 months in those who tolerated it (n = 3); however, the discontinuation rate was high due to severe injection-site reactions. Tocilizumab had a 64% response rate at 6 months (seven of 11 patients), with 36% of patients achieving complete response, whereas baricitinib showed modest effectiveness, with the highest mortality at 27%. Adverse events were documented for 54% of the therapies, with infections being the most common events, particularly noted with azacitidine (62%) and tocilizumab (47%). IN PRACTICE: 'The findings of this study provide important real-world evidence to guide clinical practice and future research directions in management of patients with VEXAS syndrome,' the authors wrote. SOURCE: This study was led by Adam Al-Hakim, BMBS, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, England. It was published online on May 21, 2025, in The Lancet Rheumatology . LIMITATIONS: The sample size was small, which affected the ability to conduct multivariable analyses, thereby affecting the assessment of treatment effectiveness. Clinical response was based on physician opinion, increasing reporting bias and variance. The lack of standardized prednisolone tapering protocols could have influenced response assessments. DISCLOSURES: No funding was received for this study. Some authors disclosed receiving honoraria, grants, travel support, and consulting fees from various pharmaceutical companies, including AstraZeneca and Novartis. One author reported receiving support for meetings, projects, advisory boards, and clinical trials from various sources.
