Upfront Therapy for ITP in Kids: New Drug a Game Changer?

Children with newly diagnosed immune thrombocytopenia (ITP) treated with eltrombopag as a frontline therapy show significantly improved platelet responses and other outcomes compared with the standard of care.

“This is the first time in 3src years that a new drug is being tested for newly diagnosed pediatric ITP,” said the study’s lead author, Kristin A. Shimano, MD, professor of pediatrics at the Benioff Children’s Hospital, University of California San Francisco, in a press statement for the study, presented at the American Society of Hematology (ASH) 2src24 Annual Meeting earlier this month.

“We really think that 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 with the goal to wean off the medication for patients who have a natural resolution of their disease,” Shimano said in her talk.

While children with ITP, a rare autoimmune blood disorder, very often improve without the need for any treatment, some do require intervention, and the condition can become chronic. First-line therapies for those patients commonly include corticosteroids, intravenous immunoglobulin (IVIg), and anti-D globulin; however, side effects can be undesirable, and with their efficacy often temporary, patients can require monitoring and juggling of treatments.

Eltrombopag, an oral, daily thrombopoietin receptor agonist, was approved by the US Food and Drug Administration for children and adults with chronic ITP in 2src15; however, research has been lacking on the benefits of the therapy for newly diagnosed pediatric patients.

To investigate the drug’s efficacy at that stage, Shimano and colleagues with the ITP Consortium of North America launched the prospective, open-label Pediatric ITP Newly diagnosed pts Epag vs Standard therapy (PINES) trial, enrolling 118 patients at 23 institutions between May 2src19 and January 2src24.

All enrollees had been diagnosed with ITP within 3 months and had been determined by their treating hematologist to require pharmacologic treatment.

Of the patients, about 4src% were untreated, and 6src% had been treated with at least one medication prior to the trial but did not have a lasting response.

The patients were stratified by age and prior treatment and randomized 2:1 to receive either eltrombopag (n=78) or the investigator’s choice of one of three standard first-line therapies, including prednisone, IVIg, or anti-D globulin at specified doses (n=4src). Overall, 29 in the standard-of-care arm received prednisone and 11 received IVIg. The patients had a median age of 8 years.

For the study’s primary endpoint, patients in the eltrombopag group had a significantly greater sustained response at 12 weeks, defined as having at least three of four platelet counts> 5src × 1src⁹/L during weeks 6-12 without the need for rescue treatment, with a rate of 63% vs 35% in the standard-of-care group (P=.srcsrc54).

There were no significant differences between the two groups in terms of the proportion of patients with a high bleeding score at weeks 1-4 and week 12.

However, those in the eltrombopag arm had a significantly lower rate of receiving rescue therapy (18% vs 38% with the standard of care; P=.src2).

Both groups showed clinically meaningful improvements from baseline in terms of health-related quality of life, as assessed by parent proxy-reported KIT overall scores.

Twenty adverse events that were grade 3 or higher, including six serious adverse events, occurred in each of the study’s arms, with the most common events including headache and epistaxis.

Treatment-related serious adverse events occurred among six patients in the eltrombopag group and one in the control group, but importantly, no thromboembolic events were reported.

One intracranial hemorrhage occurred in the eltrombopag arm.

With eltrombopag having a slower effect than some other treatments, Shimano cautioned that the therapy is not recommended for patients with severe bleeding.

“Patients with grade 4 or 5 bleeding at the time of screening were specifically excluded from the study, so for patients who have very severe bleeding who need to get their platelets up very quickly, this would not be the ideal therapy for them,” she noted.

On the basis of results, the trial was recommended to close early due to efficacy; however, the participants are being followed for a total of 12 months to determine the durability of the responses, including in terms of bleeding events, quality of life, or the development of chronic ITP.

“We have shown that in pediatric patients with newly diagnosed ITP requiring pharmacologic treatment, eltrombopag resulted in a significant, clinically relevant higher rate of a durable platelet response in the absence of rescue treatment as compared with standard first-line therapies,” Shimano said.

“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,” she added.

Commenting on the study, James B. Bussel, MD, emeritus professor of pediatrics, medicine and obstetrics and gynecology at Weill Cornell Medicine in New York City, commented that “generally, a short-term increase in platelets is the biggest challenge, which is getting the patient to the point of not requiring future treatment to get better.”

“If more children can be shown to be going into remission earlier, that would be great,” he said.

While eltrombopag is known to be effective in chronic ITP, a key caveat of its use in newly diagnosed patients is the question of whether patients will get better on their own and feasibly be able to be spared the cost and burden of treatment in the first place.

However, identifying which patients will fit that profile isn’t always easy.

“Exactly which child needs treatment can be hard to determine, and there is some debate about that,” Bussel noted.

“The theoretic standard is that the platelet count doesn’t matter — only whether the patient is bleeding a lot, and then there is debate over treatment based on bleeding scores,” he said.

Quality-of-life issues, such as patients’ ability to take part in activities, are also a key consideration.

“It would be great if eltrombopag can support children who really need it and provide clear unequivocal benefit beyond just increasing the platelet count, but also leading to better quality of life,” Bussel said.

The new findings are “a very encouraging start, but I’d really like to see what the story is at 1 year