Successful Tolerance of Deferasirox Following Desensitization for Significant Skin Rash
Authors: Ezzat Hatoon , Schellenberg R. Robert , Leitch Heather A , Vickars Linda M 
Published: October 2019

Abstract
Abstract 5280

BACKGROUND:
Deferasirox is an oral iron chelator that has become available in recent years. The long term tolerability profile of deferasirox is still being evaluated, however a common side effect is skin rash, which may occur in up to 10% of patients. This is usually mild to moderate and resolves with continued treatment. More severe rash may require interruption of therapy and reintroduction of deferasirox at a lower dose followed by gradual dose escalation. A short course of corticosteroids may be used. Occasional cases of angioedema have been reported for which cessation of deferasirox is recommended but re-introduction is difficult. We report three patients with hypersensitivity to deferasirox, two manifested as NCI CTC grade 3-skin rash and one as grade 1-skin rash. All were able to tolerate deferasirox following desensitization.

METHODS:
Two patients with β thalassaemia major and one with congenital sideroblastic anemia, all with transfusional iron overload, experienced skin rash to deferasirox and received a desensitization protocol, given orally as follows:
Solution 1 (deferasirox 1.25 mg/ml):
1 ml given days 1–3
2 ml given days 4–6
5 ml given days 7–9
Followed by Solution 2 (deferasirox 12.5 mg/ml)
1 ml given days 10–12
2 ml given days 13–15
5 ml given days 16–18
The dose of deferasirox was subsequently increased by 125 mg/day every week until the desired dose was reached.

RESULTS:

Case 1:
A 23 year-old female with b thalassaemia major, non-compliant with deferoxamine, was switched to deferasirox 1500 mg/day (20mg/kg/day). Nine days after starting deferasirox she experienced a low grade fever, extensive erythematous maculopapular rash and facial edema. Deferasirox was discontinued. Two days later the rash had progressed; prednisone was started at 50 mg/day and the rash resolved within 1 week. While still tapering prednisone (20 mg/day), deferasirox was re-started at 500 mg/day. The rash recurred within 2 days and deferasirox was discontinued. One year later the desensitization protocol was given and well tolerated without the development of skin rash; she is currently receiving deferasirox 1500 mg/day without difficulty.

Case 2:
A 21 year-old female with b thalassaemia major, non-compliant with deferoxamine, was switched to deferasirox 1500mg/day (20mg/kg/day). Ten days after starting deferasirox she developed diffuse erythema multiforme. Deferasirox was stopped and prednisone started at 1mg/kg/day with marked improvement. Five days later, still on prednisone in full doses, she was re-challenged with deferasirox 500 mg/day. The rash recurred and deferasirox was discontinued. One year later, the desensitization protocol was given and well tolerated without the development of skin rash. She is currently receiving deferasirox 1500mg/day without difficulty.

Case 3:
A 23 year-old female with congenital sideroblastic anemia receiving deferoxamine was switched to deferasirox 1500mg/day (20mg/kg/day) for ease of administration. Eight days after starting deferasirox she developed a maculopapular rash confined to the palms of the hands and soles of the feet, but associated with severe pruritis. Deferasirox was stopped and the patient declined prednisone. She resumed deferoxamine and was offered the deferasirox desensitization protocol. Desensitization was given successfully but required a three day extension of treatment with solution 1 (2ml) because of recurrent rash, which resolved over the following two days with the temporary addition of benadryl. She is currently receiving deferasirox 150mg/day on weekly dose escalation without difficulty.

CONCLUSION:
Deferasirox is often the chelation agent preferred by patients given its ease of administration. Given its documented reduction in total body iron, with promising effects on the removal of myocardial iron, the use of this agent is increasing. However, skin rash is a side effect that may limit the use of deferasirox in some patients. To our knowledge, this is the first report of a protocol that may successfully desensitize patients with hypersensitivity reactions to deferasirox, allowing them to tolerate this agent in therapeutic doses.

Disclosures:
Leitch: Novartis Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.