Options for Reducing or Discontinuing TPO-RA Therapy in ITP Patients − Expert Consensus

Questions Regarding ITP Treatment with TPO-RA

Immune thrombocytopenia is an autoimmune disease that leads to decreased platelet production and increased platelet destruction. Thrombopoietin receptor agonists induce the proliferation and differentiation of platelet precursors, i.e., megakaryocytes, resulting in increased platelet production. They are a well-established line of treatment.

It has been shown that both eltrombopag and romiplostim (i.e., drugs from the TPO-RA group) increase platelet counts and prevent serious bleeding episodes in 80–90% of patients with ITP. The response rate, published based on long-term follow-up studies, reaches 65–88%. The goal of TPO-RA therapy is not to normalize platelet counts but to increase them to a level that minimizes the risk of bleeding, typically within the range of 50–150,000/μl. In patients who maintain platelet counts within the normal range over the long term, TPO-RA doses can be gradually reduced. However, if a level of > 50,000/μl is considered safe, the question arises whether maintaining platelet counts in the range of 50,000–100,000/μl over the long term could justify dose reduction or discontinuation of TPO-RA. Clear recommendations are lacking.

Main Points of Consensus

British hematologists were surveyed about their approach to TPO-RA dose reduction or discontinuation. Using a Delphi panel, recommendations (consensus) were developed on this issue. Physicians estimated that 30–34% of their TPO-RA-treated patients were suitable for dose reduction or therapy discontinuation. Additionally, 29–35% of these patients subsequently needed to resume therapy, with an average treatment-free interval of 86–106 days. No predictors of response to dose reduction or therapy interruption were described.

According to the expert consensus on ITP, approximately 30% of ITP patients treated with TPO-RA meet the conditions under which dose reduction or therapy discontinuation can be considered. These steps can be considered after 6–12 months of treatment in patients who have shown an appropriate therapeutic response, i.e., platelet counts > 50,000/μl at more than 3/4 of visits in the past 6 months. Possible factors influencing the decision include age, duration of ITP, current TPO-RA dose, treatment duration, response dynamics, platelet counts after 6 months of therapy, and comorbidities. Factors that may increase the likelihood of remission include younger age, shorter duration of ITP, lower TPO-RA doses, shorter treatment duration, or higher achieved platelet counts at shorter intervals or lower TPO-RA doses.

Resumption of therapy may be considered if there is a decline in platelet counts (< 30,000/μl) or if the patient becomes symptomatic, experiences decreased quality of life, anxiety, or fatigue associated with ITP, which can be alleviated by restarting therapy. It is essential to consider all patient characteristics in any decision-making process.

Conclusion

In conclusion, the authors state and summarize that for a portion of ITP patients treated with TPO-RA, it is possible to consider dose reduction or therapy discontinuation. However, clear predictors of response to dose reduction or therapy termination are not yet available, and it should be anticipated that some patients may need to resume therapy. More specific insights could be provided by prospective studies focused on this issue.

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Source: Cooper N., Hill Q. A., Grainger J. et al. Tapering and discontinuation of thrombopoietin receptor agonist therapy in patients with immune thrombocytopenia: results from a modified Delphi panel. Acta Haematol 2021 Mar 31; 1–9, doi: 10.1159/000510676 [Online ahead of print].