Hydroxyurea for Children and Adults with Hemoglobin SC Disease

Area of Science:

• Hematology
• Clinical Trials
• Sickle Cell Disease

Background:

• Hemoglobin SC (HbSC) disease is a prevalent sickle hemoglobinopathy associated with severe complications and mortality.
• Currently, no established disease-modifying treatments exist for HbSC.
• This study investigated hydroxyurea as a potential treatment for HbSC.

Purpose of the Study:

• To evaluate the safety and efficacy of hydroxyurea in patients with HbSC.
• To assess hematologic dose-limiting toxicities (DLTs) as the primary endpoint.
• To examine clinical outcomes including pain events, acute chest syndrome, and hospitalizations.

Main Methods:

• A double-blind, randomized, placebo-controlled, non-inferiority phase 2 trial (PIVOT) was conducted.
• Children and adults with HbSC in Ghana received hydroxyurea or placebo for 12 months.
• Primary endpoint: hematologic DLTs; Secondary endpoints: clinical events, quality of life, organ function, and rheology.

Main Results:

• Hydroxyurea treatment led to more DLTs (33%) compared to placebo (11%), exceeding the non-inferiority margin.
• Significant reductions were observed in vaso-occlusive pain events (IRR 0.38) and hospitalizations (IRR 0.42) with hydroxyurea.
• A composite of acute sickle-related events was reduced in the hydroxyurea group (IRR 0.39) for both children and adults.

Conclusions:

• The PIVOT trial did not meet its primary endpoint for non-inferiority regarding hematologic DLTs.
• Hydroxyurea at 20 mg/kg was associated with more, though mostly mild and transient, DLTs.
• Despite increased DLTs, hydroxyurea demonstrated a significant reduction in pain and sickle-related events, warranting further investigation in new trials.