Thomas Kuehne, one of ERCI founding members, has recently edited for UNI-MED the 3rd edition of the book “Immune Thrombocytopenia (ITP)”.
The world’s leading experts in ITP contributed to the book, which encompasses all aspects of ITP (history, pathogenesis, genetics, diagnosis, treatment) in adults and children.
Other peculiar aspects of the disease are also dealth with in this very comprehensive publication, such as ITP in pregnancy, chronic refractory disease, the burden of ITP for the patients with consequences on their quality of life.
Among the authors there are other 2 ERCI members, who contributed with chapters devoted to the standardization of definitions, terminology and outcome criteria and to the management of ITP in the elderly.
From June 9th to 22nd the EHA 2022 Congress took place in Vienna.
Here a brief report concerning interesting new data on ITP.
The diagnosis of ITP remains one of exclusion, and sometimes the differential diagnosis of an isolated thrombocytopenia may be tricky, especially with regards to myelodysplastic syndromes (MDS) presenting with isolated thrombocytopenia. Gonzalez-Lopez et al. (Abstract P1647) made an attempt to distinguish these two groups by bone marrow (BM) morphology and BM next generation flow cytometry. Of the 62 evaluated patients, 53 BM samples were analyzed by cytomorphology: 18 ITP and 10 MDS have been diagnosed, the remaining cases being unclassifiable. Flow-cytometry showed alterations in all groups, without a clear distinguished pattern, but a trend towards multilineage BM alterations in the MDS and unclassified groups. The results of this study underscore the problem of the differential diagnosis of an isolated thrombocytopenia, which in a not negligible proportion of cases remains unresolved even with bone marrow examination.
Anti-platelet antibodies remain a debated tool which could be used both for ITP diagnosis and as factor predictive of response to treatment. However the role of such antibodies in clinical practice is not defined yet, mainly due to issues related to their measurement. Dong (Abstract PB2297 and PB2298) analyzed anti-platelet antibodies (GP-IIb/IIIa; GP-Ib/IX and GP Ia/IIa) by PAKauto ELISA kit in 154 newly diagnosed pediatric ITP patients treated with first-line therapy. Patients positive for anti-GP-Ib/IX had a worse response to corticosteroids +/- IvIg, and patients with anti-GP-IIb/IIIa had a more severe disease (meaning they needed a combined treatment). These reports underline another unmet need in ITP: the standardization of the antiplatelet antibody testing, which is nowadays still far from routine clinical application.
Several abstracts focused on the treatment with TPO-mimetics, in particular in view of the achievement of a sustained response off-treatment (SRoT). Cooper et al. (Abstract S292) presented the results of the phase II TAPER trial. ITP patients were treated with eltrombopag as second-line therapy, and those who achieved and maintained a complete remission for 2 months could taper down and discontinue the drug. 105 patients were enrolled, 62% met the criteria for tapering and discontinuation, and SRoT was achieved at month 12 in 30% of patients. Ghanima et al. (Abstract P1638) compared platelet responses according to the time since ITP diagnosis, and found no difference in terms of platelet response and frequency and severity of bleeding across the groups. These reports confirm the feasibility of SRoT in nearly 30% of ITP patients who start eltrombopag therapy, and point out 2 evidences: response rates to eltrombopag given earlier during the course of the disease are similar to those obtained during the chronic phase; the probability to achieve SRoT is similar in patients who start the tapering being or not in complete remission.
In order to shed light on the molecular mechanisms of eltrombopag refractoriness, Gonzalez-Lopez et al (Abstract P1639) reported the results of an NGS analysis who evaluated 108 genes related to eltrombopag mode of action, comparing 35 refractory patients to 35 controls who responded to treatment. 13 variants were significantly different between the two populations, some of them already described as associated with solid cancers, but most of them of uncertain significance, that will need further work to be established.
Among emerging treatment options in ITP, rilzabrutinib is an oral Bruton tyrosine kinase inhibitor, which has already shown its efficacy and tolerability in a phase I/II trial. Kuter et al. (Abstract S291) described the long-term extension outcomes of patients receiving the maximum dose of rilzabrutinib 400 mg twice a day. 45 heavily pretreated patients initiated treatment, platelet response was achieved in 40%. 16 patients proceeded to long-term extension, and a platelet count ≥ 50.000/mmc was maintained for the majority of the weeks of observation (a median of 88%). Of note, the majority of patients was receiving a concomitant medication (TPO-RAs +- corticosteroids).
ITP and COVID-19.
The topics of ITP secondary to or exacerbated by COVID-19 infection or vaccination have also been addressed. A report from the US PDSA (Platelet Disorder Support Association) patient registry showed that one third of ITP patients experienced a platelet count drop following either COVID-19 infection or the vaccine, generally mild and recovered within 1 month (DiRaimo et al. Abstract P1637). The British guidelines for the diagnosis and treatment of VITT (vaccine-induced thrombotic thrombocytopenia) were presented, and as well as the guidelines for COVID-19 vaccination of patients with ITP.
For the full-texts of the abstracts and other reports, visit ehaweb.org
The British Journal of Haematology has just published online ahead of print a Letter to the Editor by Moulis et al which presents the first outcomes of the ERCI research study to assess the possibility of ITP registry linkage and harmonization at a European level. This first step was to identify ITP registries across Europe and to describe their main characteristics. These results are reported here.
On Friday 6th May 2022 the “ITP Update Day”, a traditional appointment for healthcare professionals interested in ITP will take place in London.
Hosted by Dr. Nichola Cooper at the Cavendish Conference Centre, a group of International experts in ITP will meet and discuss about several aspects of the disease, with the aim to provide an overview on clinical and treatment updates, also in light of the COVID-19 pandemic.
Let’s briefly have a look at the program: the first session is dedicated to Registry Data, with updates on the UK ITP registry, the ITP Association and ITP forum; an update concerning European activities will also be provided, including those carried out by the ERCI group (the European Research Consortium on ITP).
The COVID-19 pandemic has significantly changed the clinical approach to many diseases, including ITP, especially considering the load of immunosuppression that burdens such patients. And for this reason treatment algorithms have been questioned and sometimes, at least partly, modified. An update of guidelines for first-line treatment during the pandemic will be presented, and there will be a focus on the early use of thrombopoietin mimetics, which has been in some way encouraged by the pandemic.
An entire session will deal with the topic of ITP and COVID-19, exploring the theme of Vaccines and the impact of COVID-19, the debatable use of Rituximab in COVID patients and the real-life, French experience of ITP in the COVID-19 pandemic.
Experts will also deal with complex clinical cases, that remain a challenge – sometimes impossible -for clinicians all over the world, but that represent a chance for questioning about differential diagnosis and the heterogeneous pathogenesis of the disease.
In the last few years, several novel drugs have been investigated in clinical trials with promising efficacy, and some of them have already received marketing authorization, meaning that in the next future a wide range of new molecules will be available for physicians. Many aspects concerning the introduction of these new drugs into clinical practice will be outlined along the way, and will help physicians in the choice of the best treatment modality or treatment combination for each patient.
The last session of the meeting will therefore focus on new treatments, and in particular on BTK inhibition, SYK inhibition, FcRn inhibition, and ongoing and future novel trials and observational studies.