Eltrombopag improves response for children with newly diagnosed immune thrombocytopenia
Key takeaways:
- Eltrombopag increased durable platelet response for children with newly diagnosed immune thrombocytopenia.
- Quality of life did not differ between children assigned eltrombopag or standard first-line therapy.
SAN DIEGO — Eltrombopag conferred a higher rate of durable platelet response in the absence of rescue treatments than standard first-line treatments for children with newly diagnosed immune thrombocytopenia, according to study results.
Investigators stopped the trial early due to the efficacy observed in the planned interim analysis.
The findings — presented at ASH Annual Meeting and Exposition — suggest the agent may have a viable role in this treatment setting, researchers concluded.
“This is the first time in 30 years that a new drug is being tested for newly diagnosed pediatric [immune thrombocytopenia (ITP)],” Kristin A. Shimano, MD, pediatric hematologist-oncologist and bone marrow transplant specialist at UCSF Benioff Children’s Hospital, said in a press release. “Patients who received eltrombopag during the first 3 months of their ITP diagnosis had a more sustained platelet response than patients who were treated with standard therapies. That means during this time period, kids taking eltrombopag were also likely to have a lower risk of having bleeding events.”
Background and methods
ITP is a rare autoimmune disorder that arises when the immune system attacks platelets. The resulting low platelet counts can lead to bruising or uncontrolled bleeding.
Multiple medications can help increase platelet counts among children with newly diagnosed ITP; however, the benefit those therapies confer often is temporary.
Eltrombopag, an oral thrombopoietin receptor agonist, is approved in the United States for treatment of children with chronic ITP. The agent’s efficacy for treatment of children with newly diagnosed ITP had not been established.
Shimano and colleagues conducted the randomized phase 3 PINES trial to compare the agent with standard first-line treatment for children with newly diagnosed ITP who required pharmacologic treatment.
The investigator-initiated prospective trial — sponsored by ITP Consortium of North America — enrolled 122 patients aged 1 to 17 years from 23 institutions who had been diagnosed with primary ITP within the prior 3 months.
The majority (60%) had taken at least one medication but had not derived durable benefit. The other 40% had not taken any medications for ITP prior to study enrollment.
All trial participants had platelet counts less than 30 x 109/L and required pharmacologic treatment per their treating clinician.
Researchers randomly assigned patients 2:1 to eltrombopag or investigator’s choice of one of three standard first-line therapies — prednisone, IV immunoglobulin or anti-D globulin.
Response — defined as at least three of four platelet counts exceeding 50 x 109/L during weeks 6 to 12 without rescue treatment — served as the primary endpoint.
Investigators deemed four enrolled patients as ineligible, leaving 118 children (age 1 to 5 years, n = 46; age 6 to 11 years, n = 42; age 12 to 17 years, n = 30) in the intent-to-treat analysis.
Seventy-eight received eltrombopag and 40 received standard therapy (prednisone, n = 29; IV immunoglobulin, n = 11).
Key findings
Researchers reported a higher median platelet count at enrollment in the standard treatment group (8 x 109/L vs. 4 x109/L), but higher median WHO bleeding scores at enrollment (2 vs. 1) and modified Buchanan Scale scores (3 vs. 2) in the eltrombopag group.
A significantly higher proportion of patients assigned eltrombopag achieved platelet response (65% vs. 33%; P = .0007). The data safety monitoring board subsequently recommended trial accrual be closed early due to the efficacy observed.
A comparable percentage of patients in each group had high bleeding scores at weeks 1 to 4 and at week 12.
However, a lower percentage of patients assigned eltrombopag received rescue therapy (18% vs. 38%).
Parent proxy-reported overall scores on the Kids’ ITP Tools (KIT), a questionnaire that assesses quality of life among children with ITP, showed clinically meaningful improvement at all time points in both groups. Results showed 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 eltrombopag experienced grade 3 or higher adverse events, including six serious adverse events in the first 12 weeks. Six children assigned standard treatment experienced grade 3 or higher adverse events, including three serious adverse events.
The most common adverse events included headache (3 for each group) and epistaxis (1 for eltrombopag vs. 2 for standard treatment).
Four patients assigned eltrombopag developed drug-related serious adverse events (elevated liver function tests, n = 2; headache, n = 2), compared with two assigned standard treatment (allergic reaction, n = 1; headache, n = 1). One patient assigned eltrombopag developed intracranial hemorrhage. No thromboembolic events occurred.
Per study protocol, trial participants will complete 12 months of follow-up.
“Eltrombopag could certainly be added to the medication choices hematologists consider as they are making treatment decisions with families,” Shimano said. “It is an option that could potentially raise platelets for a more sustained period in children with [immune thrombocytopenia] in the newly diagnosed period, which is one of the most difficult times for patients with regard to the impact of the disease on bleeding symptoms and quality of life.”
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Shimano KA, et al. Abstract 709. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.