Eltrombopag/eltrombopag improves response in children with newly diagnosed immune thrombocytopenia

According to study results, Eltrombopag resulted in higher rates of durable platelet responses than standard first-line therapy in children with newly diagnosed immune thrombocytopenia in the absence of rescue therapy. Researchers stopped the trial early because efficacy was observed in a planned interim analysis. These findings suggest that the drug may have a viable role in this therapeutic setting.

For the first time in 30 years that a new drug has been tested in children with newly diagnosed immune thrombocytopenia (ITP), patients who received eltrombopag within the first 3 months of diagnosis of ITP had more durable platelet responses than those who received standard care. This means that children taking eltrombopag may also have a lower risk of bleeding events during this time.

ITP is a rare autoimmune disease that occurs when the immune system attacks platelets. The resulting low number of platelets can lead to bruising or uncontrollable bleeding. Various medications help increase platelet counts in children with newly diagnosed ITP; however, the benefits of these therapies are often temporary. The oral thrombopoietin receptor agonist eltrombopag is approved in the United States for the treatment of chronic ITP in children. The drug's efficacy in children with newly diagnosed ITP has not been established.

RandomizedThe phase 3 PINES trial compared the drug with standard first-line treatment in children with newly diagnosed ITP who require medical treatment. The investigator-initiated prospective trial enrolled 122 patients aged 1 to 17 years from 23 institutions who had been diagnosed with primary ITP within the past 3 months. Most people (60%) took at least one drug but experienced no lasting benefit. Another 40% were not taking any ITP medications before study enrollment. All trial participants had platelet counts below 30x10^9/L and required medical treatment from their attending physician.

The investigators randomly assigned patients in a 2:1 ratio to eltrombopag or one of three standard first-line treatments of the investigator's choice: prednisone, intravenous immunoglobulin, or anti-D globulin. Response was defined as at least three of four platelet counts exceeding 50x10^9/L between weeks 6 and 12 without rescue therapy as the primary endpoint. The investigators considered 4 enrolled patients to be ineligible, leaving 118 children (1 to 5 years old, n=46; 6 to 11 years old, n=42; 12 to 17 years old, n=30). Seventy-eight patients received eltrombopag, and 40 received standard care (prednisone, n=29; intravenous immunoglobulin, n=11).

Researchers reported that median platelet counts were higher in the standard treatment group (8 x 10^9/L vs. 4 x 10^9/L), but the median WHO bleeding score was higher (2 vs. 1) and the modified Buchanan Scale score was higher (3 vs. 2) in the eltrombopag group. A significantly higher proportion of patients receiving eltrombopag achieved a platelet response (65% vs. 33%; P=0.0007). In light of the observed efficacy, the data safety monitoring board subsequently recommended ending trial accrual early. A significant proportion of patients in each group had high bleeding scores at weeks 1-4 and 12.

However, a lower proportion of patients receiving eltrombopag received rescue therapy (18% vs. 38%). Parent-proxy-reported overall scores on the Child ITP Instrument (KIT), a questionnaire that assesses the quality of life of children with ITP, showed clinically meaningful improvements in both groups at all time points. Results showed that there was no significant difference in mean absolute change from baseline in the eltrombopag or standard treatment groups at 1 week (8.7 vs. 10.1), 4 weeks (13.4 vs. 10.7), or 12 weeks (15.6 vs. 11.2).

Twenty children assigned to eltrombopag experienced grade 3 or higher adverse events, including 6 serious adverse events in the first 12 weeks. Six children who received standard treatment experienced grade 3 or higher adverse events, including three serious adverse events. The most common adverse events included headache (3 in each group) and epistaxis (1 in the eltrombopag group and 2 in the standard treatment group).

Four patients receiving eltrombopag experienced drug-related serious adverse events (elevated liver function tests, n=2; headache, n=2), associated with two designated standard treatments (anaphylaxis, n=1; headache, n=1). One patient receivingeltrombopag developed intracranial hemorrhage. No thromboembolic events occurred.

According to the study protocol, trial participants will complete12 months of follow-up. When eltrombopag is added to the drug selection, it is an option that may increase platelets more sustainably in children with newly diagnosed[immune thrombocytopenia], one of the most difficult times for patients in terms of the disease's impact on bleeding symptoms and quality of life.

References:https://www.healio.com/news/hematology-oncology/20241207/eltrombopag-improves-response-for-children-with-newly-diagnosed-immune-thrombocytopenia