Romiplostim in Newly Diagnosed or Persistent ITP
Thrombopoietin receptor agonists (TPO-RA) are now recommended for patients with newly diagnosed immune thrombocytopenia (ITP) or persistent ITP who have failed treatment with corticosteroids or intravenous immunoglobulins. The rationale for these recommendations is documented in a paper whose authors focus on, among other things, the American Society of Hematology (ASH) 2019 guidelines or the European ITP Working Group guidelines. They also summarized published data from clinical trials, real-world practice, etc., regarding the use of the TPO-RA romiplostim in earlier phases of ITP therapy.
Introduction
Immune thrombocytopenia is a rare autoimmune disease in which the platelet count drops below 100 × 109/l. The essence of the disease is not only the destruction of platelets but also a disturbance in their production. The primary manifestation of ITP is increased bleeding, especially cutaneous and mucosal, but there is also a risk of more serious bleeding, such as intracranial bleeding. Today, ITP is classified according to the duration into acute (up to 3 months from the first symptoms), persistent, and chronic phases (more than 12 months). With increasing duration, the chance of achieving (spontaneous) remission also decreases.
Different Goals of ITP Treatment
Different recommendations always reflect the treatment goals in different phases of ITP:
- For acute ITP, the goal is to prevent or stop bleeding and achieve remission.
- For persistent ITP, the goal is the same as in the acute phase but with a focus on minimizing the impact of long-term treatment on the patient's quality of life.
- For chronic ITP, the goal, besides achieving a safer platelet count, is mainly the patient's quality of life and minimizing the toxicity of different treatment regimens.
It always applies that achieving a certain platelet count is only part of the treatment goals.
TPO-RA in Life-Threatening Bleeding
In the case of life-threatening bleeding, the European ITP Working Group suggests considering the administration of TPO-RA or rituximab together with corticosteroids if a sufficient response to intravenous immunoglobulins (IVIG) and possibly platelet transfusions in a patient receiving corticosteroids is not achieved. Similarly, the International Consensus Report proposes the administration of TPO-RA in newly diagnosed ITP in the case of life-threatening bleeding when the classical approach is insufficient.
Early Administration of TPO-RA
Most patients respond to initial treatment with corticosteroids and/or IVIG; however, many will relapse after such treatment ends and will require additional therapy. The main common element of current recommendations is delaying splenectomy, emphasizing the use of TPO-RA or rituximab earlier during the disease course (often already after the first 3 months), which contrasts with previous recommendations where TPO-RA use was reserved mainly for the chronic phase of the disease or after splenectomy failure.
Modern recommendations mention that evidence for administering TPO-RA in adults in the earlier phase of the disease (when there is an inadequate response to corticosteroids or IVIG) is strong. Another reason for the earlier transition of patients to TPO-RA is the risk of side effects, especially with long-term corticosteroid use. Moreover, TPO-RAs are considered as a second-line modality with the highest chance of success and a favorable safety profile.
In several studies, TPO-RA romiplostim led to a clear response in terms of platelet count increase (79−95%), and these results were sustained over time. Studies also showed that romiplostim is well tolerated.
Conclusion
According to the authors of a review of 9 clinical studies, 6 real-world practice studies, and 10 case reports, early inclusion of romiplostim in adult patients with ITP can help reduce exposure to the adverse effects of corticosteroids while simultaneously decreasing the risk of serious bleeding. Moreover, given the sustained response observed in patients with newly diagnosed or persistent ITP and the potential to achieve a durable response allowing the discontinuation of TPO-RA, early use of romiplostim may help avoid the need for further sequential therapy.
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Sources:
1. Lozano M. L., Godeau B., Grainger J. et al. Romiplostim in adults with newly diagnosed or persistent immune thrombocytopenia. Expert Rev Hematol 2020; 13 (12): 1319−1332, doi: 10.1080/17474086.2020.1850253.
2. Matzdorff A., Meyer O., Ostermann H. et al. Immune thrombocytopenia – current diagnostics and therapy: recommendations of a joint working group of DGHO, OGHO, SGH, GPOH, and DGTI. Oncol Res Treat 2018; 41 (Suppl. 5): 1–30, doi: 10.1159/000492187.
3. Provan D., Arnold D. M., Bussel J. B. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019; 3 (22): 3780–3817, doi: 10.1182/bloodadvances.2019000812.
4. Neunert C., Terrell D. R., Arnold D. M. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3 (23): 3829–3866, doi: 10.1182/bloodadvances.2019000966.
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