Studies Presented at ASH 2024 Advance Thrombocytopenia Management, Etiology Understanding

Thrombocytopenia was among several blood-related disorders for which clinical research progress was showcased at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California. Investigators from around the world presented new data on the management and etiology of this disease.

The bulk of studies presented on thrombocytopenia at the Meeting concerned adult and pediatric immune thrombocytopenia. Prominent among these was the first report from the adult patient portion of the LUNA 3 phase 3, placebo-controlled, parallel-group, multicenter study. The study evaluated the oral covalent, reversible Bruton tyrosine kinase inhibitor (BTKi) rilzabrutinib for disease resistant to standard-of-care therapy.

Based on the findings, lead author David J Kuter, MD, DPhil, of Massachusetts General Hospital, Boston, with an international team of experts as coauthors, concluded that “rilzabrutinib has a robust therapeutic effect as shown by rapid and durable platelet response, reduced bleeding and need for rescue therapy, improved physical fatigue and QoL [quality of life], and favorable safety and tolerability.”¹

Coverage of pediatric disease at the Meeting included results from a phase 3 prospective, open-label, randomized, multicenter trial of eltrombopag versus standard first-line treatments. Presented was analysis of the first 12 weeks of 12-month follow-up in the intent-to-treat cohort of the Pediatric ITP Newly diagnosed pts Epag vs Standard therapy (PINES) trial, in which the experimental thrombopoietin receptor agonist was compared with prednisone, IV immunoglobulin, and anti-D globulin. The trial’s primary end point of platelet response was achieved by 65% of patients in the eltrombopag arm versus 33% of patients who received standard of care (P=0.0007).²

“In pediatric pts [patients] with newly diagnosed ITP [immune thrombocytopenia] requiring pharmacologic treatment, epag [eltrombopag] leads to a significantly higher rate of a durable platelet response in the absence of rescue treatments as compared with standard first-line therapies,” wrote lead author Kristin A Shimano, MD, of University of California San Francisco Benioff Children’s Hospital, with a team of experts from clinical centers across the United States.²

Another trial presented at the Meeting, which evaluated a novel thrombopoietin receptor agonist for thrombocytopenia, specifically assessed hetrombopag for this condition after allogeneic hematopoietic stem cell transplant (HSCT). This retrospective observational study of real-world data was conducted by researchers from Peking University Institute of Hematology, Beijing, China.

The cohort of 33 patients in the study, 87.9% of whom had undergone haploidentical donor transplantation, began oral hetrombopag treatment at a median of 56 days after transplant with a median dose of 5 mg/day for a median treatment duration of 82 days. The overall platelet response rate was 81.8%, and the investigators concluded from the results that hetrombopag has real-world utility for increasing platelet levels in patients with thrombocytopenia after allogeneic HSCT.³

Also reported at the Meeting was research advancing understanding of thrombocytopenia etiology, including chemotherapy-induced thrombocytopenia (CIT) by Andrew B Song, MD, and Hanny Al-Samkari, MD, of Massachusetts General Hospital, Boston, with Brian Curtis, PhD, D(ABMLI), MT(ASCP) SBB, of Versiti Platelet and Neutrophil Immunology and Hematology Genetics Labs, Milwaukee, Wisconsin.

In an observational study, these 3 investigators evaluated adults with solid tumor malignancies and CIT for the presence of direct glycoprotein-specific platelet autoantibodies. They expected amounts to be low in this population, but their high-fidelity assay testing returned significantly positive findings.⁴

“These results are consistent with known immune dysregulation in cancer patients receiving cytotoxic chemotherapy and raise provocative questions regarding a potential immune-mediated mechanism of thrombocytopenia in many patients with CIT,” the investigators concluded.⁴

Regarding cyclic thrombocytopenia (CTP), the findings reported at the Meeting from a study that evaluated data from both a patient cohort and a clinical database support low variant allele frequency (VAF) STAT3 gain-of-function (GOF) mutations and clonal T cells as risk factors for the disease.

“This study provides additional evidence that subclonal (VAF<10%) STAT3 GOF mutation and T-cell clonality correlate with CTP. While clinically significant CTP requiring interventions is rare, our database review suggests that clinically silent perturbations of thrombopoiesis in these patients are more prevalent than previously appreciated,” concluded first author Haiyu Zhang, PhD, of Stanford University, California, and colleagues.⁵

References

1. Kuter DJ, Ghanima W, Cooper N, et al. Efficacy and safety of oral Bruton tyrosine kinase inhibitor (BTKi) rilzabrutinib in adults with previously treated immune thrombocytopenia (ITP): a phase 3, placebo-controlled, parallel-group, multicenter study (LUNA 3). Abstract #5. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.
2. 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. Abstract #709. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.
3. Ma R, Luo X, Sun W, et al. Evaluation of the real-world efficacy of hetrombopag for the treatment of thrombocytopenia post allogeneic hematopoietic stem cell transplantation. Abstract #2160. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.
4. Song AB, Curtis B, Al-Samkari H. Direct glycoprotein-specific platelet autoantibodies detected in a majority of patients with chemotherapy-induced thrombocytopenia. Abstract #1180. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.
5. Zhang H, Stehr H, Bona RD, et al. Correlation of low variant allele frequency STAT3 gain-of-function mutations and T-cell clonality with cyclic thrombocytopenia. Abstract #1175. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.