Real-world study: How should elderly patients with ITP use TPO receptor agonists?

Research highlights preview thrombopoietin receptor agonists (TRA) Eltrombopag and Romiplostim are effective in elderly patients with primary immune thrombocytopenia (ITP) without fatal bleeding , And 13.
8% of patients continued to respond after stopping treatment
.

A history of thrombosis and no secondary anti-thrombotic prevention are related to thrombosis and recurrence during treatment
.

Research background ITP is a rare acquired immune disease characterized by a platelet (PLT) count of <100×109/L and an increased risk of bleeding
.

Children and the elderly are the two peak ages of ITP, and the incidence of ITP among the elderly increases with age
.

Elderly patients are often weaker, poorer in physical condition, and have a variety of comorbidities that need to be controlled by drugs
.

Previous studies have shown that elderly patients with ITP have a more aggressive course, a higher risk of bleeding at diagnosis, and a corresponding increase in the risk of thrombosis and infection during follow-up
.

Eltrobopar and Romigrastim are TRA, and most patients with ITP can obtain platelet responses through their treatment
.

At present, the efficacy and safety of TRA in elderly patients with ITP are still unclear
.

Based on this, some researchers analyzed the response of ITP patients ≥60 years of age to TRA treatment, as well as the conversion of different TRA types, the risk of thrombosis/bleeding, and the patient's sustained response to treatment discontinuation (SROT)
.

Research method ELDERLY-ITP-TRA is an observational retrospective study that included ITP patients ≥60 years old who were treated with TRA from 16 medical centers in Italy according to standard clinical practice
.

ITP is defined as platelet count <100×109/L without other reasons
.

TRA failures include persistent thrombocytopenia (platelet count ≤30×109/L for 4 consecutive weeks) under the highest recommended dose of TRA, discontinuation of TRA due to adverse events (AE), and death due to TRA treatment or ITP-related causes
.

Sustained response to discontinuation of treatment (SROT) is defined as the response time without any remedial drugs during the period from TRA stopping to the disappearance of the response or the last follow-up
.

Study Results 01 Study population The study finally included 384 eligible patients, and all patients were followed up until death or the data cut-off date for this analysis (November 1, 2020)
.

The main demographic and hematological characteristics of the study cohort are shown in Table 1
.

The median follow-up time of patients receiving TRA treatment was 2.
7 years.
A total of 7 patients (1.
8%) were due to uncontrollable diabetes (N=3) or other complications (N =4) And the first line receives TRA treatment
.

In addition, 59 patients (13.
4%) received rituximab before TRA treatment; a total of 82 patients (21.
4%) had at least one thrombotic event before TRA treatment
.

The most common comorbidities in the patients in this study were diabetes, solid tumors, and acute myocardial infarction
.

Table 1 The main demographic and hematological characteristics of the study population 02 First TRA treatment options and platelet reaction situation In this study, 271 cases (70.
6%) of the patients used TRA for the first time, and 113 cases (29.
4%) were used for the first time.
The TRA used was Romipristine; Elderly patients with ITP used TRA for the first time more frequently (P=0.
03)
.

At the beginning of TRA treatment, elderly patients ≥75 years of age used concomitant ITP therapy (glucocorticoids and/or immunoglobulins) at a higher rate than patients <75 years of age (P=0.
02), but they used Eltrodopa and Luo The frequency of use of concomitant therapy was similar in patients treated with Mimistin (P=0.
97)
.

The median duration of the first TRA treatment was 1.
2 (0.
1-11.
4) years, which was similar in all age groups
.

Overall, 255 of the 337 evaluable patients (75.
7%) achieved platelet response at 2 months, and 264 (80%) of 330 evaluable patients achieved platelet response at 3 months; and in two At the time point, 42.
7% and 46.
7% of the patients achieved complete remission (CR), respectively
.

66.
7% of patients in remission continued to remission until the last follow-up, and the median duration of remission was 2.
1 years, regardless of the patient’s age and remission status at 2 months
.

Incidence and risk factors of 03TRA failure.
Overall, 96 patients (25%) failed TRA treatment
.

The cumulative failure rate at 1 year was 18.
4%, and the failure rates of patients treated with Eltroipopag and Romiprist were comparable
.

The reasons for TRA failure include non-response (57.
3%) and TRA treatment-related AEs (42.
7%)
.

The results of univariate analysis showed that only the absence of early response may increase the risk of patients with TRA treatment failure (P=0.
05)
.

(Figure 1) Figure 1 Results of univariate analysis of TRA treatment failure in patients 04 Thrombosis and bleeding during TRA treatment The incidence of thrombosis during TRA treatment was higher than before the start of TRA (P<0.
001), and the same was true when only major thrombosis was considered
.

The incidence of bleeding during TRA treatment was higher than before the start of TRA (P=0.
01)
.

05 Discontinuation of treatment and SROT situation Overall, 62 of the 384 patients (16.
5%) discontinued TRA treatment due to stable efficacy, and the median time from the start of TRA to discontinuation was 0.
9 years (range: 0.
4-10.
2)
.

There was no significant difference in the incidence of discontinuation due to sustained remission between different TRAs
.

At the last follow-up, 53 patients (13.
8%) maintained SROT and the median duration of remission was 1.
3 years (range 0.
03-9.
6)
.

SROT is not affected by the patient's age, gender, TRA type, timing of starting TRA treatment, platelet count at the beginning of TRA treatment, and comorbidities
.

The duration of TRA treatment <6 months has nothing to do with SROT
.

SROT was more common in patients who discontinued TRA treatment because the curative effect reached CR (P<0.
001)
.

06 Overall survival of patients In this study, 43 patients (11.
2%) died of non-ischemic heart disease (13.
9%), thrombosis (11.
6%), solid tumors (14%), and age-related multiple organ failure (23.
3) %) and other non-ITP related reasons (18.
6%)
.

Overall, the median survival (OS) of patients was not reached, and the OS rate at 3 years was 89.
8%.
Patients under 75 years of age had a higher OS rate than patients ≥75 years of age (94.
9% vs 82.
1%, log-rank P=0.
002), and the patient’s gender, type of TRA received, and platelet reaction at 2 or 3 months had no significant effect on OS
.

Research conclusions TRA is effective and safe for elderly patients with ITP, without fatal bleeding, and some patients have achieved SROT
.

The risk of thrombosis still exists, and the risk/benefit balance between thrombosis and bleeding events should be carefully considered before prescribing TRA
.

For ITP patients with clear indications for TRA, high risk of thrombosis, and no bleeding risk factors other than ITP, whether anti-thrombotic prevention should be performed requires further research
.

If the patient can safely begin antithrombotic secondary prevention, then the continuation of TRA treatment should not be prevented after a thrombotic event
.

Reference source: Palandri F.
, Rossi E.
, Bartoletti D.
, et al.
Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia.
Blood (2021) 138 (7): 571–583.
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