Eltrombopag Bests Standard of Care as First-Line Therapy in Pediatric Immune Thrombocytopenia

Data from the PINES trial indicate children with newly diagnosed immune thrombocytopenia (ITP) receiving eltrombopag could achieve better outcomes with eltrombopag (Promacta) than with standard first-line therapies.

Presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, the trial findings suggest use of eltrombopag was associated with a significantly greater rate of a durable response in the absence of rescue treatments relative to standard first-line therapies, which included prednisone, Intravenous immunoglobulin (IVIG), or anti-D globulin at specified doses.1

“This is the first time in 30 years that a new drug is being tested for newly diagnosed pediatric ITP,” said lead investigator Kristin A. Shimano, MD, professor of pediatrics at the University of California, San Francisco Benioff Children’s Hospital.2 “Patients who received eltrombopag during the first three 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.”

A oral thrombopoietin receptor agonist, eltrombopag first received approval from the US Food and Drug Administration in 2008 as the first oral agent awarded an indication for treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura.3

Launched 4 years after the FDA approval of eltrombopag in adults and children with chronic ITP in 2015, the PINES trial was an endeavor conducted by the ITP Consortium of North America to assess the safety and efficacy of eltrombopag as a first-line therapy in pediatric ITP. A prospective, open label, randomized trial conducted at 23 medical centers, the study enrolled 118 patients diagnosed with ITP less than 3 months prior to enrollment and who required pharmacologic treatment in the opinion of their treating hematologist.1,2

Among the 118 patients, 46 were aged 1 to 6 years, 42 were aged 6 to 12 years, and 30 were aged 12 to 18 years. At enrollment, the median platelet count was 4 × 10⁹/L (range, 1 to 23) in the eltrombopag arm and 8 × 10⁹/L (range, 1 to 28) in the standard of care arm.1

Investigators noted 40% of the study cohort had not yet taken any medications for ITP before enrolling while the other 60% had taken at least 1 medication but not seen a lasting benefit. Investigators pointed out those with a history of prior medication were not randomized to the same medication after enrollment.1

Study participants were randomized in a 2:1 ratio, with stratification by age and prior treatment status, to eltrombopag or standard of care.1

The primary outcome of interest for the study was sustained platelet response at 12 weeks, which investigators defined as having 3 or 4 platelet counts higher than 50 x 109/L during weeks 6 to 12 without additional treatment.1

Result of the primary endpoint analysis indicated platelet response was achieved by 65% patients of the eltrombopag arm and 33% of the SOC arm (P = .0007). Further analysis suggested rescue therapy was received among 19% of the eltrombopag arm and 46% of the standard of care arm (P = .002).1

When assessing quality of life changes, results indicated the mean absolute change from baseline in parent-proxy reported KIDS ITP Tool scores appeared to favor eltrombopag relative to standard of care at 1 week (P = .45), 4 weeks (P = .24), and 12 weeks (P = .14). Investigators pointed out these differences were consistent with a clinically meaningful improvement in quality of life at all time points in both arms.1

“Eltrombopag could certainly be added to the medication choices hematologists consider as they are making treatment decisions with families, and it is an option that could potentially raise platelets for a more sustained period in children with ITP 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,” Shimano added.2

References:

1. Shimano KA, Grimes AB, Rose MJ, et al. Efficacy Findings in a Phase 3, Randomized Trial of Eltrombopag Vs. Standard First-Line Treatment for Newly Diagnosed Immune Thrombocytopenia in Children. Presented at: 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10; San Diego, California.
2. American Society of Hematology. Putting women and children first to optimize their Hematology Health. Hematology.org. December 7, 2024. Accessed December 8, 2024. https://www.hematology.org/newsroom/press-releases/2024/putting-women-and-children-first-to-optimize-their-hematology-health.
3. US Food and Drug Administration. Drug approval package. Promacta (Eltrombopag) NDA #022291. Accessed December 8, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm.