The phase 2 LODEFI study, presented at the 2024 ASH Annual Meeting & Exposition, reveals that low-dose deferasirox (Jadenu) can effectively induce transfusion independence (TI) in patients with low-risk anemia associated with myelodysplastic syndrome (MDS). The multi-center, open-label trial (NCT03387475) highlights a potential new treatment avenue for patients who have relapsed or are refractory to erythropoietin-stimulating agents (ESAs).
Efficacy of Deferasirox in MDS-Related Anemia
At 12 months, 47.4% (95% CI, 31.0%-64.2%) of patients treated with deferasirox achieved transfusion independence. When applying a stricter definition—a transfusion burden of 4 or more red blood cell units every 8 weeks—68.4% (95% CI, 51.3%-82.5%) of patients achieved TI at 12 months.
According to lead study author Dr. Sophie Park, a professor at the Centre Hospitalier Universitaire de Grenoble, "There is still an unmet medical need for patients with low-risk MDS who are refractory or relapsing to erythropoietin agents [ESAs] and transfusion dependent." She further noted that low-dose deferasirox could be a viable treatment option for selected MDS patients with low transfusion burden who have not responded to ESA therapy.
The study met its primary endpoint, demonstrating the efficacy of low-dose deferasirox on transfusion dependence at 12 months, defined as needing two or more red blood cell units per 8 weeks for a total of 24 weeks between months 6 and 12 from treatment initiation. A key secondary endpoint, replicating the primary one with more intensive requirements, defined TI at 12 months as a burden of more than 4 red blood cells units every 8 weeks for 24 weeks. The biological and clinical tolerability of low-dose deferasirox was also assessed.
Study Design and Patient Population
The trial enrolled 38 patients with very low (n = 16), low (n = 19), and intermediate (n = 1) MDS, based on the Revised International Prognostic Scoring System and 2016 World Health Organization (WHO) Guidelines. These patients were either refractory or relapsing to ESAs, had a low transfusion burden, and a ferritin level under 1000 µg/l. All patients received 3.5 mg/kg of deferasirox orally each day for 12 months, with dosage adjustments at month 1 to reach approximately 3 µM by month 3. All patients had prior ESA treatment.
The median age of the enrolled patients was 73.5 years (IQR, 69.0-78.0), and the median Charlson Comorbidity Index was 4.0 (IQR, 3.0-5.0). MDS subtypes, based on 2016 WHO guidelines, included MDS-single lineage dysplasia (SLD) (21.1%), MDS-multilineage dysplasia (MLD) (36.8%), MDS-RS (21.1%), chronic myelomonocytic leukemia (CMML)-1 (2.6%), MDS with excess blasts (MDS EB)-1 (7.9%), and unclassifiable MDS (MDS-U) (10.5%). The median ferritin level at inclusion was 547.0 µg/L (IQR, 399.0-849.0), and the median hemoglobin level was 86.0 g/L (IQR, 81.0-97.0). Most patients (86.8%) were non-transfusion dependent per the International Working Group 2018 criteria, while 13.2% had a low transfusion burden.
Safety and Tolerability
Low-dose deferasirox was generally well-tolerated. Treatment discontinuations occurred due to renal and hepatic impairment, and one patient experienced a deferasirox overdose due to diabetes. Adverse effects were primarily grade 1 to 3 and included digestive, auditory, and renal issues.
Notably, patients with MDS-RS showed a lower rate of transfusion dependence compared to other MDS subtypes, with 28.6% vs. 58.3%, respectively, according to the primary endpoint definition.
