Working toward international consensus defining pediatric “refractory ITP”

TO THE EDITOR:

We, as the Pediatric Immune Thrombocytopenia (ITP) Consortium of North America (ICON) have received the response¹ to our recent article, “What is in a name: defining pediatric refractory ITP,”² from the Coagulation Disorder Working Group of the Pediatric Hematology-Oncology Italian Association (AIEOP). This, along with the AIEOP’s recent consensus publication,³ indicates clear agreement regarding the need to update and standardize our terminology for symptomatic ITP which fails to respond to multiple therapies.

Efforts to test the functionality of our proposed “refractory” definitions included evaluation of platelet nonresponse in a cohort of children (n = 511) diagnosed with ITP at a single ICON institution during a recent 5-year period (2019-2023). Among these patients, 325 (64%) received treatment with at least 1 emergent therapy and 95 (19%) received treatment with at least 1 disease-modifying therapy. Among those receiving emergent therapy, 2.5% were considered “refractory” according to the proposed definition (no platelet response after treatment with all eligible emergent pharmacotherapies)² and among those receiving disease-modifying therapy, 7% showed no response to 2 or more different classes (Table 1). Notably, the rate of chronicity among those with ITP “refractory to emergent therapy” was only 25%; vs 100% in those with ITP “refractory to disease-modifying therapy.” Consortium-wide efforts are planned to further evaluate this terminology’s correlation to risk of disease persistence and burden within a multi-institutional cohort of children categorized by these treatment response–based definitions.

Table 1.

Pediatric patients with ITP "refractory" to emergent and disease-modifying therapies

Patients receiving 1 or more emergent therapy (IVIG, corticosteroids, or anti-D), n = 325	n	%
Response to at least 1 therapy	279	86
No response to 2 or more therapies	18	6
No response to all eligible therapies∗	8	2.5
Patients receiving 1 or more disease-modifying therapy†, n = 95	n	%
Response to at least 1 disease-modifying therapy	87	92
No response to 2 or more classes of disease-modifying therapy	7	7

IVIG, intravenous immune globulin; anti-D, anti-D immune globulin.

^∗All eligible therapies include all drugs available in the patient’s institution, for which they are clinically eligible (ie, patients with known Rh+ blood group status who have no clinical evidence of hemolytic anemia, in the case of anti-D therapy).²

^†Disease-modifying therapy is the use of pharmacotherapy agents (eg, thrombopoietin-receptor agonists, biologics, and immunomodulating agents) and interventions (eg, splenectomy) to achieve a sustained, durable maintenance response in platelet count to prevent ongoing exacerbations of symptomatic ITP and improve quality of life.²

We agree that the importance of identifying this subset of children with “refractory ITP” is to accurately and expeditiously identify patients who would benefit from early escalation of therapy, expanded evaluation, and consideration for clinical trials and ITP research. We propose a unified effort to define “refractory ITP” terminology and to validate an international consensus definition, in hopes of improving outcomes for children with this challenging disease phenotype across the world.

Conflict-of-interest disclosure: A.B.G. reports research support from Novartis. R.J.K. reports consultancy fees from Agios, Amgen, Bayer Canada, Hoffmann-La Roche, Novo Nordisk, Octapharma AG, Sanofi, and Takeda. M.P.L. serves on advisory boards for Octapharma AG, Dova, Principia, Rigel, Argenx, Platelet Disorder Support Association, 22q Society, and Cornelia de Lange Syndrome Foundation; reports consultancy fees from Agios, Novartis, Dova, Principia, Argenx, Rigel, Sobi, Sanofi, and Janssen; and reports research support from the Foundation for Women and Girls with Bleeding Disorders, the Platelet Disorder Support Association, National Institutes of Health, Sysmex, Novartis, Principia, Argenx, Dova, Octapharma AG, and Sanofi. C.N. reports research support from Novartis, and consultancy fees from Novartis, Argenx, Sanofi, and Sobi. K.A.S. reports research support from Novartis, Sobi, and Sanofi. R.F.G. reports research support from Novartis, Sobi, and Agios, and consultancy fees from Agios and Sanofi.