Results of a Prospective Phase II Randomized Study of Deferasirox (Exjade®) to Prevent Iatrogenic Iron Overload in Patients Undertaking Induction/Consolidation Chemotherapy for Acute Myeloid Leukaemia (HREC/10/QRBW/135)

Iron overload, as measured by raised serum ferritin, is recognised as a significant risk factor for excess transplant related mortality (TRM) in allogeneic stem cell transplantation (SCT). Due to blood transfusions received during initial induction/consolidation chemotherapy, almost all patients undertaking SCT with AML have significantly raised ferritin pre-SCT.

To determine the efficacy of deferasirox (Exjade®) in preventing iatrogenic iron overload in patients receiving induction/consolidation chemotherapy for AML.

Prospective randomised phase II study in AML patients planned to receive induction and/or consolidation chemotherapy. Iron studies and CRP were measured pre, mid and post each chemotherapy cycle. Patients were randomised to receive either therapy with deferasirox (starting at 5–10mg/kg/day PO and increasing to maximum 40mg/kg/day PO as tolerated) vs. no deferasirox therapy. Desferasirox was commenced once ferritin increased to >500μg/L and continued until transfusion independence after completion of all chemotherapy. The primary endpoint was ferritin concentration at completion of chemotherapy. Based on historical controls, to detect a difference of >1000μg/L in ferritin between groups a sample size of 14 per arm was required.

The study was terminated prematurely after 16 patients were enrolled (deferasirox arm n=10; control arm n=6) due to excess grade 2–4 GIT (frequency 1.26 vs. 0.75 events/chemotherapy cycle for deferasirox vs. control arm respectively; p=0.04) and infectious toxicity (frequency 2.22 vs. 1.38 events/chemotherapy cycle for deferasirox vs. control arm respectively; p=0.05) experienced in the deferasirox arm. Overall desferasirox was poorly tolerated, with mean maximum tolerated dose only 13.2mg/kg/day (range 5–20mg/kg/day) and 4/10 patients unable to continue the drug predominantly due to GIT toxicity. Post-treatment ferritin, % change in ferritin and number of transfusions received were no different between arms. Post-chemotherapy CR rate was lower in the desferasirox arm (60% vs. 100%; p=0.234), and all treatment-related deaths (n=3; all infectious-related) occurred in the desferasirox arm (p=0.25). Median OS was similar in both arms (median 450 vs. 476 days for deferasirox vs. control arm respectively; p=0.72).

Use of desferasirox to prevent iatrogenic iron overload in AML patients undertaking induction/consolidation is ineffective, poorly tolerated, and associated with excess GIT and infectious toxicity.

No relevant conflicts of interest to declare.