TY - JOUR
T1 - Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia
T2 - Real-world recommendations
AU - Zaja, F.
AU - Carpenedo, M.
AU - Baratè, C.
AU - Borchiellini, A.
AU - Chiurazzi, F.
AU - Finazzi, G.
AU - Lucchesi, A.
AU - Palandri, F.
AU - Ricco, A.
AU - Santoro, C.
AU - Scalzulli, P. R.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Thrombopoietin receptor agonists (TPO-RAs) are currently indicated for continuous treatment of chronic primary immune thrombocytopenia (ITP). However, there is growing evidence that TPO-RAs can also trigger sustained response in 10–30% of cases after treatment tapering and discontinuation. Therefore, at least for selected responding patients, it might be rational to plan TPO-RA interruption to exploit off-treatment response. Intriguingly, complete or partial responses with TPO-RAs are frequently observed when treatments are initiated early, suggesting that unknown immune-related mechanisms may be involved in this phenomenon. The sustained responses observed after interruption of TPO-RAs may be interpreted as a recovery of immunological tolerance; thus, the re-establishment of immunological equilibrium might be primarily responsible for the observed off-treatment effect. Importantly, these findings may indicate that anticipated TPO-RA usage can lead to improved responses, and that optimized tapering and interruption in selected patients can furthermore improve prognoses. On the base of this rationale, a series of real-life considerations have been generated by a panel of Experts to elucidate possible novel criteria and modalities to identify subgroups of patients who can benefit from tapering and/or discontinuation of TPO-RAs. Towards this aim, the results of a survey of ITP experts are herein reported, reflecting a snapshot of current real-life experience on early discontinuation of TPO-RA-based therapy. The present manuscript also highlights the importance of future translational studies on novel prognostic and predictive biomarkers that can stratify patients and facilitate the clinical choice for second-line treatment of ITP.
AB - Thrombopoietin receptor agonists (TPO-RAs) are currently indicated for continuous treatment of chronic primary immune thrombocytopenia (ITP). However, there is growing evidence that TPO-RAs can also trigger sustained response in 10–30% of cases after treatment tapering and discontinuation. Therefore, at least for selected responding patients, it might be rational to plan TPO-RA interruption to exploit off-treatment response. Intriguingly, complete or partial responses with TPO-RAs are frequently observed when treatments are initiated early, suggesting that unknown immune-related mechanisms may be involved in this phenomenon. The sustained responses observed after interruption of TPO-RAs may be interpreted as a recovery of immunological tolerance; thus, the re-establishment of immunological equilibrium might be primarily responsible for the observed off-treatment effect. Importantly, these findings may indicate that anticipated TPO-RA usage can lead to improved responses, and that optimized tapering and interruption in selected patients can furthermore improve prognoses. On the base of this rationale, a series of real-life considerations have been generated by a panel of Experts to elucidate possible novel criteria and modalities to identify subgroups of patients who can benefit from tapering and/or discontinuation of TPO-RAs. Towards this aim, the results of a survey of ITP experts are herein reported, reflecting a snapshot of current real-life experience on early discontinuation of TPO-RA-based therapy. The present manuscript also highlights the importance of future translational studies on novel prognostic and predictive biomarkers that can stratify patients and facilitate the clinical choice for second-line treatment of ITP.
KW - Corticosteroids
KW - Immune thrombocytopenia (ITP)
KW - Long-term response (R)
KW - Real-life
KW - Tapering
KW - Thrombopoietin receptor agonists
UR - http://www.scopus.com/inward/record.url?scp=85076241228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076241228&partnerID=8YFLogxK
U2 - 10.1016/j.blre.2019.100647
DO - 10.1016/j.blre.2019.100647
M3 - Review article
AN - SCOPUS:85076241228
JO - Blood Reviews
JF - Blood Reviews
SN - 0268-960X
M1 - 100647
ER -