Addressing Characteristics, Response and Relapse: Eltrombopag As Third Line in Primary and Secondary Immune Thrombocytopenia

Introduction:

Eltrombopag is used as a second line treatment in patients with primary immune thrombocytopenia (ITP). There is little information, and its use is uncertain in secondary immune thrombocytopenia (sIT), and as a third line of treatment.

Aim:

To evaluate the differences in response and relapse in patients who received eltrombopag with ITP or sIT after two or more lines of treatment.

Material and methods:

Retrospective study that included patients with ITP and sIT who received eltrombopag after two or more lines of treatment in a reference center in Mexico City from 2022 to 2024. Descriptive statistics, the Chi square test or Fisher's exact test, the T-test and the U Mann-Whitney test were performed.

Results:

A total of 27 patients were included; 18 (66.6%) with ITP and 9 (33.3%) with sIT due to a connective tissue disease (CTD). In the group with sIT the main CTD were: systemic lupus erythematosus in 5 (55%) patients, antiphospholipid syndrome in 2 (22%) patients, and rheumatoid arthritis and systemic sclerosis each one in 1 (11%) patient, respectively.

The majority were women with 22 (81.5%) patients. The median age at diagnosis was 26 (range: 11-62) years and 37 (range: 18-74) years at the start of eltrombopag.

Regarding first-line treatment, all patients received steroids, and 9 (33.3%) received intravenous immunoglobulin. Patients from both groups received a second-line treatment, and 25 (92.6%) received more than two lines, with a median number of relapses of 3 (range: 2-4) before starting eltrombopag. Splenectomy was performed in 16 (59.3%) patients; 10 (37%) were before receiving treatment with eltrombopag.

Regarding responses with eltrombopag as a next line of treatment; 3 (11.1%) patients had a partial response (PR) with a median of 19.5 (range: 7-34.7) days and 24 (88.9%) a complete response (CR) with a median of 27.5 (range: 14-59.5) days. Those with PR had a higher mean platelet count (MPC) at diagnosis of 27 + 13.8 x 10⁹/L vs 13.9 + 6 x 10⁹/L than those with a CR (p = 0.027).

The mean maximum platelet count achieved was 113.2 + 61.6 x 10⁹/L in a median of 44 (range: 22-91) days. A total of 14 (51.9%) patients received eltrombopag at doses of 50 mg/day and 13 (48.1%) patients received 75 mg/day.

Differences were found when comparing patients with sIT vs ITP. At diagnosis they had a lower hemoglobin of 11 + 3.1 g/dL vs 13.4 + 1.9 g/dL (p = 0.015), lower lymphocyte counts of 960/mm³ (range: 720-1545) vs 1640/mm³ (range: 1169-2925) (p = 0.022), and greater mean platelet volume of 11 fL (range: 10.7-12.1) vs 10.5 fL (range: 9.6-10.9) (p = 0.033).

Relapse with the use of eltrombopag occurred in 22 (81.5%) patients with a MPC of 24.5 + 12.7 x 10⁹/L and median days to relapse of 128 (range: 48-414). Relapse cases were attributed to the fact that 8 (36%) patients discontinued eltrombopag with a median days of treatment of 179 (range: 47.2- 1118), and 8 (36%) due to dose modification. Relapse occurred in patients with more than two lines of prior treatment (p = 0.028).

The 100% of ITP patients had a relapse vs 44.4% of patients with sIT (p = 0.002). The median of days to relapse was 195 (range: 83-486) in ITP and 34.5 (range: 8.5-56) in sIT (p = 0.014). In the non-relapse group, all patients had sIT (p = 0.002) and had been treated with dexamethasone (p = 0.048) in the first line.

Regarding complications, 8 (29.6%) presented thrombocytosis, 5 (18.5%) major bleeding, 2 (7.4%) previous thrombosis due to the CTD before starting eltrombopag, and 27 (100%) mucocutaneous bleeding.

Conclusion:

Time to PR, CR and maximum response with eltrombopag were similar in ITP and sIT. Patients with PR presented higher platelet counts at diagnosis. There were differences in blood cell counts at diagnosis in both groups.

The majority of patients with relapse had suspension or dose modification of eltrombopag and have received more than two lines of treatment. Less than half of patients with sIT had a relapse, and it presented in a shorter time than patients with ITP.

Eltrombopag could be an effective alternative in patients with sIT because of CR as well as a lower relapse rate. There is concern about thrombosis in cases of CTD; however, it was not identified in our study as being associated with the use of eltrombopag. Although eltrombopag was started in third line it remained effective with prolonged durations of response.

No relevant conflicts of interest to declare.