In a multicenter trial, deferasirox reduced serum ferritin and labile plasma iron (LPI) in transfusion-dependent patients with myelodysplastic syndrome (MDS). A subset of patients also experienced improvements in hematologic parameters.
In spite of these results, nearly 80% of patients discontinued therapy. But researchers said only about 40% of the discontinuations were drug-related; ie, a result of adverse events, abnormal lab values, or drug inefficacy.
Alan F. List, MD, of the Moffitt Cancer Center in Tampa, Florida, and his colleagues reported these results in the Journal of Clinical Oncology. The team’s research was supported by Novartis Pharmaceuticals, the maker of deferasirox.
The researchers analyzed the effects of the drug in 173 patients with low- or intermediate-1-risk MDS. The median patient age was 71 years (range, 21 to 90 years).
Patients had serum ferritin of at least 1000 μg/L, had received at least 20 units of red blood cells, and had ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg per day, with dose escalation up to 40 mg/kg per day.
Patients who completed 1 year of therapy (n=91) experienced a median decrease in serum ferritin of 23%. Serum ferritin decreased by 36.7% in patients who completed 2 years of therapy (n=49) and 36.5% in patients who completed 3 years of therapy (n=33).
The investigators measured LPI quarterly during the first year of the study. Nearly 40% of patients (n=68) had elevated LPI at baseline. But, by week 13, LPI levels had normalized in all of the patients.
Twenty-eight percent of patients (n=51) experienced hematologic improvements according to International Working Group 2006 criteria. However, 7 of these patients had received growth factors or MDS therapy.
By the end of the study period, 79.8% of patients (n=138) had discontinued therapy. The reasons included adverse events in 24.8% (n=43), death in 16.1% (n=28), administrative problems in 15.4% (n=27), and abnormal lab values in 13.2% (n=23).
In addition, 6.9% of patients (n=12) chose not to enroll in the extension phase of the study, and 1.7% of patients (n=3) reported an unsatisfactory therapeutic effect. In 1.1% of cases (n=2), the patient no longer required the drug.
The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. Of the 28 patient deaths, none were linked to deferasirox.
“Overall, this study demonstrated improvements in iron parameters in a group of heavily transfused, lower-risk patients with MDS,” Dr List said. “A randomized trial is warranted to better ascertain the clinical impact of deferasirox therapy in lower-risk patients with MDS.”
