One thousand patients with ET: Patient characteristics, management, and clinical outcomes

Essential thrombocythemia (ET) is a Philadelphia-chromosome-negative myeloproliferative neoplasia which is characterized by the abnormal proliferation of megakaryocytes in the bone marrow resulting in thrombocytosis.¹

Gangat et al.¹ and Loscocco et al.² conducted retrospective studies documenting the patient characteristics, management strategies and clinical outcomes of 1,000 patients with ET at single centers in the United States (US) and Italy, respectively. The MPN Hub is pleased to summarize the results of these studies, with comparisons made between the two geographical centers.

Patient characteristics^1,2

• In both the US and Italian cohorts:
  • ET was more commonly observed in female patients than male (63% vs 37% and 65% vs 35% of patients, respectively); and
  • cardiovascular risk factors were observed in over 50% of the patients.
• Extreme thrombocytosis, defined by a platelet count ≥1,000 × 10⁹/L, was more commonly observed in the US cohort than in the Italian clinic with a prevalence of 26% vs 16%, respectively.

Additional patient characteristics, by region, are shown in Figure 1.

*Data from Gangat, et al.¹ and Loscocco, et al.²

Driver mutations

Janus kinase 2 gene mutations are the most common driver mutation in myeloproliferative neoplasms, accounting for 62% and 66% of patients with ET in the US and Italian centers. Across both centers the distribution of driver mutations was comparable (Figure 2) with the order of most common mutations in both being:

1. Janus kinase 2 mutation
2. Calreticulin mutation
3. Triple-negative
4. Myeloproliferative leukemia

CALR, calreticulin; JAK, Janus kinase; MPL, myeloproliferative leukemia.
*Data from Gangat, et al.¹ and Loscocco, et al.²

Treatment at diagnosis^1,2

In both centers, initial treatment following diagnosis was comparable. The most common initial treatment in both cohorts was antiplatelet therapy (90%) or specifically aspirin (81%) in the US followed by cytoreductive therapy administered to >50% of patients (Figure 3).

*Data from Gangat, et al.¹ and Loscocco, et al.²

• Aspirin was identified to reduce the recurrence of arterial thrombosis
• Treatment with cytoreductive therapy was also found to be related to a reduced incidence of:
  • venous thrombosis, hazard ratio 0.3 (p = 0.01); and
  • arterial thrombosis, hazard ratio 4 (p = 0.04).

Outcomes^1,2

Overall survival

• The risk factors identified for poorer overall survival were similar in both clinics with older age being most consistently associated with shorter survival periods.
• The impact of geographic location and risk factors on overall survival was also similar between cohorts (Table 1).

Table 1. Hazard ratios for overall survival by risk factor and geographic location*

*Data from Gangat, et al.1 and Loscocco, et al.2
Hazard ratio	US clinic (n = 1,000)	Italian clinic (n = 1,000)
Male gender	1.8	1.9
Absolute neutrophil count	1.6	1.8
Absolute lymphocyte count	1.5	1.2
Hypertension	1.7	–
Arterial thrombosis history	1.7	–

• The mortality rate during the follow-up period was 17% in the Italian center and 28% in the US.
• The most common causes of death in both groups included blast transformation, infection, thrombosis, solid tumors, major hemorrhage, heart failure, myelofibrosis, dementia, renal failure, hepatic failure, injury, and graft-versus-host disease.

Survival data over time, by region, is presented in Table 2.

Table 2. Overall survival in patients with ET by region*

ET, essential thrombocythemia; OS, overall survival. *Data from Gangat, et al.1 and Loscocco, et al.2
Survival, % (unless otherwise specified)	US clinic (n = 1,000)	Italian clinic (n = 1,000)
Median OS, years	20.6	27.1
10-year OS	81	86
20-year OS	52	64
30-year OS	25	43

Conclusion

The trends in characteristics, management strategies and outcomes for patients with ET were generally consistent across the two geographical regions.  Data from additional regions would enable further development of the reference bank, aiding in treatment development and ensuring representation of patient cohorts in pivotal clinical trials.