Deferiprone on par with deferoxamine for kids with rare anaemias

In a subgroup analysis of the phase IV FIRST trial presented at ASH 2021, the oral iron chelator deferiprone was comparable to the infusion-administered deferoxamine in terms of efficacy and safety in iron-overloaded children receiving chronic transfusion therapy for sickle cell disease (SCD) and other anaemias.

“Children with SCD who have their disease managed with frequent blood transfusions often require iron chelation therapy to prevent iron overload,” said Dr Mona Hamdy from the Cairo University Faculty of Medicine, Cairo, Egypt, who presented the findings.

“Deferoxamine is an iron chelator approved for paediatric use that is often administered via infusion. However, adherence to treatment in paediatric populations is a key challenge experienced by patients and caregivers due to the burdensome nature of the administration route,” Hamdy continued.

In the initial findings, deferiprone – which has been approved in the US as first-line treatment for transfusional iron overload in paediatric and adult patients with SCD, thalassaemias, and other anaemias – was noninferior to deferoxamine in patients with SCD and iron overload (as assessed by liver iron concentration [LIC]) and has an acceptable safety profile. [Blood 2019;134(Suppl 1):618]

“[In the current analysis,] deferiprone is also comparable to deferoxamine in reducing LIC in paediatric patients,” Hamdy said.

LICs dropped from baseline levels with both deferiprone and deferoxamine at 6 months (mean change, –1.72 vs –1.49 mg/g dry weight [dw]), more so at 12 months (mean change, –3.39 vs –2.99 mg/g dw). A comparison between arms did not yield any significant difference at both timepoints (p=0.66 and p=0.57 at 6 and 12 months, respectively). [ASH 2021, abstract 762]

No new safety issues

Despite the numerically different rates of adverse events (AEs) between the deferiprone and deferoxamine arms, the differences were not statistically significant (13 percent vs 2 percent; p=0.10 [severe AEs], 23 percent vs 12 percent; p=0.16 [serious AEs], and 6 percent vs 0 percent; p=0.17 [withdrawals owing to an AE]).

One child on deferiprone withdrew from the study due to developing agranulocytosis after 234 days. However, the patient recovered 4 days following withdrawal.

Elevated liver enzyme levels were significantly higher with deferiprone vs deferoxamine (10 percent vs 0 percent; p=0.03 for both ALT and AST*). “[Nonetheless, this is] a known transient reaction to deferiprone that typically resolves with continued deferiprone therapy,” Hamdy noted. Indeed, apart from one case of AST that remained elevated, all cases resolved.

The most common AEs of any severity in ≥5 percent of the study population were pyrexia (34 percent [deferiprone] and 36 percent [deferoxamine]) and bone pain (31 percent and 38 percent, respectively).

To improve adherence, outcomes

This subgroup analysis comprised 128 children (mean age 10 years, 58 percent male) from the FIRST study cohort. Participants were randomized 2:1 to receive either oral deferiprone 25–33 mg/kg TID or SC deferoxamine 20–40 mg/kg/day 5–7 days a week for 12 months. The main inclusion criteria was a diagnosis of iron overload and an LIC of >7–30 mg/g dw. More than three-quarters of participants had transfusion-dependent SCD (78 percent), while the rest had other anaemias (eg, spherocytosis, congenital dyserythropoietic anaemia, and other rare anaemias).

“[In] real-life practice, oral chelators are definitely more acceptable among children than deferoxamine, because it affects the psychological relationship between the child and [the parent, as the latter] is the one causing pain [due to the route of administration],” explained Hamdy. “[To avoid this], both the patient and parents usually prefer oral chelators than deferoxamine.”

“Thus, the present findings may benefit children and their healthcare providers when considering an effective iron chelation therapy that … could improve treatment adherence and outcomes,” concluded Hamdy.