The role of thrombopoietin receptor agonists in the management of adult primary immune thrombocytopenia – a single center experience

Marijana Virijević; Mirjana Mitrović; Nikola  Pantić; Zlatko  Pravdić; Nikica Sabljić; Nada Suvajdžić-Vuković

doi:10.2298/VSP210721090V

Marijana Virijević University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia https://orcid.org/0000-0003-4626-4215
Mirjana Mitrović University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia https://orcid.org/0000-0001-8313-3754
Nikola Pantić University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia https://orcid.org/0000-0001-7798-4026
Zlatko Pravdić University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia https://orcid.org/0000-0001-5095-7327
Nikica Sabljić University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia https://orcid.org/0000-0001-5488-126X
Nada Suvajdžić-Vuković University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia https://orcid.org/0000-0002-8807-4797

DOI: https://doi.org/10.2298/VSP210721090V

Keywords: eltrombopag;, purpura, thrombocytopenic, idiopathic;, receptors, thrombopoietin;, romiplostim;, treatment outcome.

Abstract

Background/Aim. The availability of thrombopoietin receptor agonists (TPO-RA) for treating primary immune thrombocytopenia (ITP) has transformed its management over the last decade. The aim of this study was to assess the efficacy of TPO-RA in adults with chronic ITP treated at the University Clinical Center of Serbia. Methods. A total of 28 adult ITP patients (10 males and 18 females), who were given eltrombopag and/or romiplostim, were enrolled in the study. Data on demographic characteristics, ITP duration, previous therapeutic modalities, comorbidities, concomitant therapy both for comorbidities and ITP, indications for TPO-RA, bleeding episodes before and during TPO-RA, TPO-RA doses, adverse events, and response rates were collected from the patients’ medical records. TPO-RAs were administered in patients with chronic refractory ITP when splenectomy was contraindicated/unfeasible and as preparation for splenectomy. Favorable treatment response was defined as a stable platelet count ≥ 50 × 10⁹/L. Results. A total of 22 (78.57%) and 14 (50.0%) patients were treated with eltrombopag and romiplostim, respectively. A good treatment response (GTR) was achieved in 81.8% of the patients receiving eltrombopag and 71.4% of those treated with romiplostim. The non-responders to eltrombopag (4 patients) and those who had lost their response to eltrombopag (4 patients) were switched to romiplostim. Six of 8 patients achieved a GTR. At the time of TPO-RA initiation, 46.4% of the patients used concomitant ITP therapy, which was ceased in all those with a GTR. The following adverse effects of TPO-RA were registered: transaminitis and transient ischemic attack for eltrombopag – one patient each, and pulmonary embolism in one romiplostim-treated patient. Conclusion. Our study showed that TPO-RAs are an effective and safe treatment option since the majority of patients achieved stable remission without bleeding episodes.

Author Biography

Nada Suvajdžić-Vuković, University Clinical Center of Serbia, Clinic for Hematology, Belgrade, Serbia

Načelnik Odeljenja za mešovite hematološke bolesti, Klinike za hematologiju, Univerzitetski klinički centar Srbije, Beograd, Srbija

Redovni profesor Medicinskog fakulteta Univerziteta u Beogradu

References

1. Provan D, Newland AC. Current Management of Primary Immune Thrombocytopenia. Adv Ther 2015; 32(10): 875‒87.

2. Rodeghiero F, Stasi R, GernsheimerT, Michel M, Provan D, Arnold DA, et al. Standardization of terminology, deﬁnitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113(11): 2386‒93.

3. Matzdorff A, Meyer O, Ostermann H, Kiefel V, Eberl W, Kühne T, et al. Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTI. Oncol Res Treat 2018; 41(Suppl 5): 1‒30.

4. Nørgaard M, Cetin K, Maegbaek ML, Kristensen NR, Ghanima W, Bahmanyar S, et al. Risk of arterial thrombotic and venous thromboembolic events in patients with primary chronic immune thrombocytopenia: a Scandinavian population-based cohort study. Br J Haematol 2016; 174(4): 639‒42.

5. Terrell DR, Reese J, Branesky D, Lu K, Watson SI, Thachil J, et al. Depression in adult patients with primary immune thrombocytopenia. Am J Hematol 2016; 91(10): E462‒3.

6. Abrahamson PE, Hall SA, Feudjo-Tepie M, MitraniGold FS, Logie J. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haematol 2009; 83: 83–9.

7. Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019; 3(22): 3780–817.

8. Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3(23): 3829–66.

9. Al-Samkari H, Kuter DJ. Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia. TherAdvHematol 2019; 10: 2040620719841735.

10. European Medicines Agency. Nplate. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/nplate. [accessed 2021 July 11].

11. European Medicines Agency. Revolade. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/revolade. [accessed 2021 July 11].

12. Medicines and Medical Devices Agency of Serbia (ALIMS). Nplate. https://www.alims.gov.rs/ciril/files/lekovi/smpc/515-01-00232-17-001.pdf. [accessed 2021 July 11]. (Serbian)

13. Medicines and Medical Devices Agency of Serbia (ALIMS). Revolade. Available from: https://www.alims.gov.rs/wp-content/
/>blogs.dir/2/files/lekovi/smpc/515-01-3507-10-001.pdf. [accessed 2021 July 11]. (Serbian)

14. Zhang J, Liang Y, Ai Y, Li X, Xie J, Li Y, et al. Eltrombopag versus romiplostim in treatment of adult patients with immune thrombocytopenia: A systematic review incorporating an indirect-comparison meta-analysis. PLoS One 2018; 13(6): e0198504.

15. González-Porras JR, Mingot-Castellano ME, Andrade MM, Alonso R, Caparrós I, Arratibel MC, et al. Use of eltrombopag after romiplostim in primary immune thrombocytopenia. Br J Haematol 2015;169(1): 111‒6.

16. Lozano ML, Mingot-Castellano ME, Perera MM, Jarque I, Campos-Alvarez RM, González-López TJ, et al. Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment-free responses, and thrombotic events in immune thrombocytopenia. Sci Rep 2019; 9(1): 16680.

17. Zaja F, Carpenedo M, Baratè C, Borchiellini A, Chiurazzi F, Finazzi G, et al. Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Rev 2020; 41: 100647.

18. Bussel JB, Saleh MN, Vasey SY, Mayer B, Arning M, Stone NL. Repeated short-term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP). Br J Haematol 2013; 160: 538‒46.

19. Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count. Haematologica 2005; 90(6): 829‒32.

20. Doobaree IU, Newland A, McDonald V, Nandigam R, Mensah L, Leroy S, et al. Primary immune thrombocytopenia (ITP) treated with romiplostim in routine clinical practice: retrospective study from the United Kingdom ITP Registry. Eur J Haematol 2019; 102(5): 416‒23.

21. Gonzalez-Porras JR, Bastida JM. Eltrombopag in immune thrombocytopenia: efficacy review and update on drug safety. Ther Adv Drug Saf 2018; 9(6): 263‒85.

22. Mitrović M, Virijević M, Pravdić Z, Pantić N, Sabljić N, Suvajdžić-Vuković N. The current role of splenectomy in the treatment of adult primary immune thrombocytopenia. Serb J Med Chamber 2020; 1(1): 57‒65. (Serbian, English)

23. Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, et al. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica 2017; 102(8): 1342‒51.

24. Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373(9664): 641‒8.

25. Kuter DJ, Tarantino MD, Lawrence T. Clinical overview and practical considerations for optimizing Romiplostim therapy in patients with immune thrombocytopenia. Blood Rev 2021; 49: 100811.

26. Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica 2019; 104(6): 1112‒23.

27. Kuter DJ, Bussel JB, Newland A, Baker RI, Lyons RM, Wasser J, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol 2013; 161(3): 411‒23.

28. Khellaf M, Viallard JF, Hamidou M, Cheze S, Roudot-Thoraval F, Lefrere F, et al. A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia. Haematologica 2013; 98(6): 881–7.

29. Cantoni S, Carpenedo M, Mazzucconi MG, De Stefano V, Carrai V, Ruggeri M, et al. Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers. Am J Hematol 2018; 93(1): 58‒64.