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Beta-thalassemia (尾-thalassemia) is a genetic blood disorder requiring regular blood transfusions. These transfusions, while life-saving, lead to iron overload, a serious complication that can damage organs. Iron chelation therapy is therefore critical for improving long-term outcomes in patients with 尾-thalassemia.

So, how effective are the 3 currently available iron chelators, deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX)? A recent study by Musallam and colleagues, published in the journal Blood Cells, Molecules and Diseases, aimed to find out. The data they report offer much-needed insights into real-world, long-term management of 尾-thalassemia.¹

Patient characteristics and study design

The researchers conducted a retrospective analysis of 663 transfusion-dependent patients with 尾-thalassemia who remained on the same iron chelator monotherapy for 10 years. The study population was well-balanced, with participants being a median age of 31.8 years at baseline, including 120 children under age 18 and 331 females (49.9%).
Patients were divided into 3 groups based on the iron chelation medication they received during the 10-year observation period: DFO (n=84), DFP (n=151), and DFX (n=428).

Patients on DFO were older, more likely to be female, and had more health problems at the study start compared to the other groups. Doses and compliance varied between the medications, with DFP having the highest compliance (96.9%), followed by DFX (97.6%) and DFO (87.6%).

Which drug produced the greatest benefit?

All 3 chelators effectively reduced serum ferritin, which is a marker of total body iron stores. There was a significant decline in serum ferritin levels over 10 years for all patient groups, with median reductions of -170.7 ng/mL for DFO (P=.049), -236.7 ng/mL for DFP (P=.001), and -323.7 ng/mL for DFX (P<.001).

Overall, the greatest improvement was seen in patients treated with DFX. The percentage of patients with serum ferritin levels <1000 ng/mL increased from 37.9% to 59.7%, and decreased from 19.2% to 11.8% (P<.001) for those with levels >2500 ng/mL. However, after adjusting for factors that included age, sex, treatment center, annual iron intake, active morbidities, and pretransfusion hemoglobin, the study did not find a definitive link between chelator type and the combined outcome of morbidity and mortality.

All 3 iron chelation therapies have minimal impact on liver function, with all groups showing improvement. However, DFX may have a slightly greater impact on kidney function compared to DFO and DFP.

There were no significant changes in liver iron concentration or cardiac T2* values over 10 years. This could be due to the study participants generally having low iron levels in these organs at baseline, suggesting that chelation therapy prevented further iron accumulation. DFX may be more effective than DFP or DFO at reducing iron stores in patients with 尾-thalassemia, but more research is needed to confirm this finding.

Key clinical associations are reported

Because all 3 chelators were comparably effective at reducing serum ferritin levels and managing overall iron burden in 尾-thalassemia patients, the study suggests these medications may be most effective in preventing further iron accumulation, rather than rapidly removing existing iron deposits from organs like the liver and heart. This highlights the importance of early diagnosis and treatment initiation to prevent significant organ damage.

DFX may offer a survival advantage, as the survival benefit in this study was statistically significant compared to DFO and warrants further investigation. As an oral medication, DFX may improve patient adherence compared to the injectable DFO. An individualized treatment approach remains crucial, however, since the results do not clearly support a single best chelator.

鈥淥ur study is in general agreement with previous real-world data of smaller cohorts from the U.S., Europe, or Asia, which often showed the ability of the 3 iron chelators to reduce or maintain iron levels at varying magnitudes, although no common pattern favoring one iron chelator over others could be observed鈥攁lthough this can be largely attributed to the observational nature of such comparisons, including those in our study,鈥� Musallam and colleagues stated in their report.¹

Limitations and conclusions

Although the investigation revealed some promising evidence supporting the long-term effectiveness of iron chelation, the study has some limitations:

• The results may not apply to all areas of the world, as the study focused on patients in Western countries with good access to healthcare resources.
• Only patients who stayed on the same iron chelation medication for the entire 10- year study period were included in the analysis. Patients who switched medications or used combination therapy were not accounted for, which may not represent the outcomes for patients with more-severe iron buildup.
• Many patients did not have magnetic resonance imaging scans to measure iron levels in the liver and heart. This might be because they had lower iron levels and did not need yearly monitoring. However, this reflects real-world decisions healthcare providers must make when managing the disease.

Independent of these limitations, this study provides valuable data on the effectiveness of different iron chelators in 尾-thalassemia. All 3 options significantly reduce levels of serum ferritin, suggesting their ability to manage overall iron burden. Given this new data, clinicians now have a clearer picture of how these therapies perform in a real-world setting, aiding in individualized treatment decisions for 尾-thalassemia patients.

Published: September 23, 2024