Double or triple therapy in newly diagnosed immune thrombocytopenia: Improving outcomes from the west-central Mexican experience. Free

Introduction

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by a low platelet count resulting from platelet destruction and impaired platelet production, involving macrophages and B and T lymphocytes. ITP has an incidence of 2 to 5 per 100 000 and can be an isolated primary condition or it may be secondary to other conditions. ITP is a heterogeneous disorder with variable clinical symptoms and remains a diagnosis of exclusion of other causes of thrombocytopenia. Many studies have been conducted during the last 2 decades investigating the efficacy and safety of combining drugs with different mechanisms of actions. Investigated approaches involves targeting autoreactive B or T cells and megakaryocytes. The rationale for combining is mainly to improve response and/or remission rates, the disadvantages include higher cost and the potential for increased toxicity. (Blood Adv 2019;3:3829-3866 and Hematology Am Soc Hematol Educ Program 2024;1:678-684).

Objectives

Report the results from combining dexamethasone and eltrombopag (DE) with or without azathioprine (DEA) in newly primary ITP adults requiring treatment.

Material and Methods

Prospective study from January 2021 to December 2024 to evaluate the efficacy and safety of two regimens in adult patients with primary ITP requiring treatment as recommended by 2019 ASH Guidelines were randomized to receive DE or DEA. Treatment consisted of oral or IV dexamethasone 40 mg daily for 4 days every 21 days for two cycles; eltrombopag 50 mg daily for 28 days, suspended if platelet counts rise above 400x10⁹/L; and azathioprine 2 mg/kg/day for 42 days in DEA arm. Primary end points were complete response (CR) and response (R), secondary end points were time to response (TTR) and duration of response DOR, all as defined by 2009 IWG Standardization. Patients were excluded if they had active infection, pregnancy, malignant disease, receiving anticoagulation or antiplatelet therapy. Complete blood count was performed at baseline, on days 3, 5, 7 and then weekly for 2 months, every two weeks until month 6 and monthly thereafter.

Results

One hundred and three patients were included; median age was 36 years (18-67); DE arm 51, 35 females and 16 males (2.1/1); DEA arm 52, 37 females and 15 males (2.4/1). Median platelet count was 5x10⁹/L (0-24). Median days of eltrombopag in both arms was 17 (13-28). At end of treatment all patients (100%) in both groups had response; with 48 (94%) CR in DE arm and 51 (98%) in DEA arm. TTR in both arms was 8 days. DOR in patients evaluated at 180 and 360 days were 44% and 23% in DE arm and 67% and 52% in DEA arm. No serious adverse effects were recorded in both arms.

Conclusions

We use a double or triple drug therapy to have more control in the pathophysiology of ITP. The use of two cycles of dexamethasone with eltrombopag gives high rates of response as in the group with the addition of azathioprine. With this latter group the DOR was better at 180 and maintained at 360 days. The cornerstone in the treatment has been with steroids, but differences in type of steroid and number if cycles remain unanswered, even more with combinations, and the introduction of new agents (Blood Reviews 2025,101300). Multicentric clinical trials are needed to evaluate the combined therapy that will bring long lasting complete remissions or even cure in the first line of therapy.