New Phase II Trial Data Support Low-Dose Deferasirox for Anemia in Low-Risk MDS

The LODEFI phase II clinical trial has evaluated the effect of low-dose deferasirox on transfusion burden in patients with low-risk myelodysplastic syndromes (MDS) resistant to erythropoietin stimulating agents (ESAs). It was presented at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

Trial coauthor Sophie Park, MD, PhD, of Grenoble Alpes University Hospital, France, wrote “[l]ow dose deferasirox induces 47.4% of transfusion independency at month 12 in low risk MDS anemic patients refractory or relapsing to ESA, with a favorable tolerance profile.”

LODEFI was a prospective, multi-center, open-label, single arm trial which enrolled 38 patients with MDS. This cohort had a median age of 73.5 years, was 57.9% male, and had a median Charlson index of 4. The revised International Prognostic Scoring System assessed 16 patients as having very low risk disease, 19 low risk, one intermediate, and was not applicable for two patients.

All patients in the cohort had low transfusion burden and ferritin levels under 1,000 µg/l. Their median hemoglobin level at inclusion was 86 g/L and median ferritin level was 547µg/L. Following the 2018 International Working Group criteria, 86.8% of the cohort was non-transfusion dependent and 13.2% had low transfusion burden.

The cohort received oral deferasirox daily for 12 months, dosed at 3.5 mg/kg at trial inclusion, with residual dosages performed at month one to adapt dosage at month three to approximately 3µM. Dosage was decreased in 26.3% of the patients and increased in 15.8% over the treatment period.

The authors reported that at 12 months, 47.4% of the cohort had achieved transfusion independence, or 68.4% of the cohort if applying a stricter definition of transfusion dependence. They noted that in patients who had MDS with ring sideroblasts, attainment of transfusion independence was less prevalent than in other MDS subtypes, at 28.6% versus 58.3%.

Regarding safety results, low-dose deferasirox was well tolerated overall by the cohort, with adverse events primarily grade 1 to 3 digestive and auditive renal reactions. Treatment was discontinued in one patient with diabetes due to an overdose of the agent leading to renal and hepatic impairment.

Dr. Park concluded that low-dose deferasirox “could be a potential treatment option for anemia in selected MDS patients who are refractory or relapsing to ESA and with low transfusion burden.”

Reference

Meunier M, Thepot S, Nimubona S, et al. A phase 2 prospective study evaluating low-dose deferasirox in patients with low-risk myelodysplastic syndrome resistant or relapsing after erythropoietin stimulating agents (LODEFI). Abstract #1826. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.