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SAN DIEGO -- Treatment with eltrombopag (Promacta) for pediatric patients with newly diagnosed immune thrombocytopenia (ITP) led to a significantly higher rate of durable platelet response compared with standard first-line therapies, an interim analysis of a phase III trial showed.

Of the initial 108 treated children, a significantly higher proportion of those randomized to receive eltrombopag rather than standard therapy met the study's primary endpoint of platelet response (63% vs 35%, respectively, P=0.0054), reported Kristin A. Shimano, MD, of the University of California San Francisco Benioff Children's Hospitals.

The z-score for the superiority of eltrombopag versus standard of care was 2.78, which crossed the pre-defined efficacy monitoring boundary, Shimano said during a press briefing ahead of the American Society of Hematology annual meeting. The data and safety monitoring board "therefore recommended early closure of the trial for efficacy," she noted.

Ten additional patients were enrolled prior to study closure, resulting in a total enrolled cohort of 118 patients. Among those patients, the primary endpoint -- defined as at least three of four platelet counts >50 × 10⁹/L without rescue treatment during weeks 6 through 12 -- was met by 65% of those in the eltrombopag arm compared with 33% in the standard care arm.

"This has the potential to transform the approach to the management of ITP in the newly diagnosed phase, with the use of a therapy that can provide sustained hemostatic platelet counts to bridge the time that patients are at risk of bleeding events until natural resolution of the disease," Shimano said.

Pediatric ITP is a rare bleeding disorder affecting 5 to 10 per 100,000 children annually. Many of the patients often experience spontaneous remission within 6 to 12 months of diagnosis and can be safely observed until remission.

"However, some children require treatment for bleeding symptoms, which can include oral bleeding, nose bleeds, menorrhagia, or more severe, life-threatening bleeding," Shimano explained. "Patients may also require treatment because of the severe impact the disease has on their quality of life due to activity restrictions due to bleeding risk from low platelet counts."

While eltrombopag, a small-molecule non-peptide thrombopoietin receptor agonist, has been approved for children with chronic ITP, its efficacy in newly diagnosed pediatric ITP is unknown. Thus, the objective of this study was to evaluate eltrombopag compared with standard therapy (intravenous immunoglobulin, prednisone, or anti-D immunoglobulin) in newly diagnosed patients.

The open-label multicenter enrolled children at least 1 year of age with newly diagnosed primary ITP, who required upfront pharmacologic treatment. Patients were randomized 2:1 to eltrombopag or investigators' choice of one of the standard therapies.

Median age at enrollment was 7.9 years in the eltrombopag group and 8.7 years in the standard therapy group, 54% and 45% were girls, respectively, and the median platelet counts were 4 × 10⁹/L and 8 × 10⁹/L. The median Modified Buchanan Bleeding Score (range 0-5, with higher scores indicating more serious bleeding) at enrollment was 3 in the eltrombopag arm and 2 in the standard therapy arm.

A little over a third of patients in both groups had received upfront treatment before enrollment, and 63% of both groups had experienced treatment failure.

Regarding the trial's secondary outcomes, Shimano reported that the proportion of patients who received rescue therapy was lower in the eltrombopag arm than the standard therapy arm (18% vs 38%, P=0.02), while the proportion of patients with a high bleeding score was similar at all timepoints in both arms.

A composite endpoint of platelets >30 × 10⁹/L with at least a twofold increase from baseline and no bleeding was achieved earlier in the standard treatment group (14 days vs 21 days in the eltrombopag arm). However, Shimano noted that 66% of patients in the eltrombopag group maintained this composite endpoint at week 12 compared with 43% of the standard therapy group.

There were 14 grade ≥3 adverse events (including six serious adverse events) in the eltrombopag arm compared with six (three serious adverse events) in the standard therapy arm. The most common adverse event was headache. Health-related quality of life improved in both arms.

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