Using the International Working Group Criteria in Thrombocytopenia Treatment, with Waleed Ghanima, MD

Most clinical trials investigating treatments for immune thrombocytopenia (ITP) aim for an overall platelet count above 50 before a patient is considered to have achieved durable response. This measurement is explicitly requested by regulatory agencies such as the US Food and Drug Administration (FDA). In 2010, however, an international group published an International Consensus Report on the investigation and management of ITP, which provided an alternative endpoint of platelet counts ≥30.1

This alternative measurement, called the International Working Group (IWG) criteria, was updated in 2019, incorporating the perspective of patients. Given the lower platelet count requirement and the comparative safety of the IWG criteria, many clinicians use this measurement rather than the 50-platelet count in their practices.1

Investigators from the ongoing phase 3 LUNA3 trial, which is examining the efficacy of rilzabrutinib in treating patients with persistent or chronic ITP versus placebo, have analyzed the modified durable response for rilzabrutinib based on IWG criteria. The results, presented at the 2025 International Society for Thrombosis and Haemostasis Congress in Washington, DC, indicated not only the efficacy of rilzabrutinib, but the comparative safety and clinical value of the IWG criteria.2

LUNA3 was divided into 2 major components; a 12-24 week double-blind treatment period, during which participants were randomized 2:1 to rilzabrutinib or placebo, and a 28-week open-label period, which saw all patients formerly receiving placebo crossover to rilzabrutinib.3 The IWG study investigated both components separately.

The investigators analyzed 133 patients given rilzabrutinib and 69 given placebo during the double-blind period of LUNA3. A collective 41% of rilzabrutinib recipients versus 9% of placebo recipients achieved a modified durable response (P <.0001). Of the 180 patients included in the open-label segment of LUNA3, 56% overall achieved modified durable response, with non-significant differences by initial double-blind assessment (53% rilzabrutinib versus 60% placebo; P = .37). Higher responses were seen in patients receiving rilzabrutinib across periods, and the trend favored patients with fewer prior ITP therapies.2

Waleed Ghanima, MD, head of research and a consultant hematologist at Østfold Hospital in Norway and the presenter of these data at ISTH 2025, sat down with HCPLive to discuss the IWG criteria and how they were used to reinterpret the topline results from LUNA3.

“The difference between the International Working Group criteria and the original is that the IWG criteria is more clinically meaningful and safe and aims to guide treatment decisions and reduce bleeding risk,” Ghanima told HCPLive. “That’s what we use in everyday practice. The 50 criteria is used by regulatory authorities like the FDA and EMA. They require these criteria, which are usually used by all studies, so it’s easier to compare studies and results of various medications across different studies.”

Ghanima led the study utilizing the IWG criteria in LUNA3; he spoke on the comparative practicality of this measurement in everyday clinical practice.

“At the end of the day, it’s what we use when we treat a patient. If the patient gets a platelet count of 45, we are happy with that.” Ghanima said. “We keep that patient on the medications, so it’s a very practical endpoint that expresses the real efficacy of the drug rather than the 50.”

References

1. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812

2. 2: Platelet responses per IWG criteria for LUNA3 rilzabrutinib vs placebo in primary ITP patients. Presented at the 2025 International Society of Thrombosis and Haemostasis Congress in Washington, DC, June 21-25, 2025.

3. Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic immune Thrombocytopenia (ITP) (LUNA 3). ClinicalTrials.gov identifier: NCT04562766. Updated on February 10, 2025. Accessed July 24, 2025. https://clinicaltrials.gov/study/NCT04562766