Eltrombopag Increases Platelet Counts in Patients with Lower-Risk MDS and Thrombocytopenia

For the 10 percent of patients with lower-risk myelodysplastic syndromes (MDS) who experience severe thrombocytopenia, there are few options for therapies to increase platelet counts. Eltrombopag, an oral agonist of the thrombopoietin-receptor that has been approved by the U.S. FDA for the treatment of idiopathic thrombocytopenic purpura (ITP), has been suggested as a potential treatment for these patients, but its efficacy has yet to be determined.

According to a recent study evaluating its safety and efficacy in inducing platelet responses in patients with low and intermediate-1 risk (according to the International Prognostic Score System [IPSS]) MDS with severe thrombocytopenia, eltrombopag may lead to significant improvement in platelet counts and fatigue (a common symptom of MDS).

Esther Natalie Oliva, MD, of the Azienda Ospedaliera Bianchi-Melacrino-Morelli in Reggio Calabria, Italy, and colleagues presented the interim results of the phase II, multicenter, prospective, placebo-controlled, single-blind study at the ASH annual meeting last month.

A total of 70 patients were randomized 2:1 to receive:

  • Eltrombopag: starting dose of 50 mg once-daily, with 50 mg increases every 2 weeks until a maximum 300 mg dose (n=46)
  • Placebo (n=24)

Adult patients were eligible for study inclusion if they had platelet counts <30 x 109/L and had an Eastern Cooperative Oncology Group performance status of <4. The mean patient age was 68.3 years, and 38 percent of participants were male.

In patients with baseline platelet count >20 x 109/L, response was defined as absence of bleeding and an increase in platelets of ≥30 x 109/L from baseline. In patients with baseline platelet count <20 x 109/L, response was defined as a platelet increase to >20 x 109/L and an increase by at least 100 percent (not due to platelet transfusion). Complete response was defined as a platelet count ≥100 x109/L and an absence of bleeding.

At the time of this interim analysis, 23 patients (50%) receiving eltrombopag had responded to treatment, compared with two patients (8%) receiving placebo (p=0.016). The median time to response was 14 days, and the median dose was 75 mg.

The platelet count increased by a mean of 53.2 x 109/L in patients receiving eltrombopag, while patients in the placebo cohort have demonstrated no significant change in platelet counts by 24 weeks of treatment. Eltrombopag treatment also improved several measures of quality of life, according to responses to a questionnaire evaluating MDS-specific symptom burden (TABLE).

Eltrombopag appeared to be well tolerated, with patients experiencing the following treatment-related grade 3 or 4 adverse events:

  • Nausea (n=4)
  • Hypertransaminasemia (n=3)
  • Hyperbilirubinemia (n=1)
  • Sepsis (n=1)
  • Pruritus (n=1)
  • Heart failure (n=1)
  • Asthenia (n=1)
  • Vomiting (n=1)

One patient in the placebo group experienced grade 3 bone marrow fibrosis.

“The drug appears to be well tolerated and not significantly associated with MDS progression,” Dr. Oliva reported, though five eltrombopag-treated patients (11%) experienced MDS disease progression, compared with two patients in the placebo group (8%).

“Preliminary data indicate that lower-risk MDS patients with severe thrombocytopenia undergoing treatment with eltrombopag experience significant improvements in platelet counts accompanied by improvements in fatigue,” Dr. Oliva and colleagues concluded. However, further follow-up is required to evaluate the effect on survival, she added.


Oliva EN, Santini V, Alati C, et al. Eltrombopag for the treatment of thrombocytopenia of low and intermediate-1 IPSS risk myelodysplastic syndromes: interim results on efficacy, safety and quality of life of an international, multicenter prospective, randomized trial. Abstract #91. Presented at the ASH Annual Meeting, December 5, 2015; Orlando, Florida.

TABLE. Quality-of-Life Comparison for Eltrombopag Versus Placebo at Baseline and 12 Weeks Post-Treatment
Quality-of-Life Measure Eltrombopag Placebo
Baseline (median, out of 100) 12 Weeks (median, out of 100) Baseline (median, out of 100) 12 Weeks (median, out of 100)
Physical 50 62 62 37
Functional 50 33 61 44
Social 50 50 50 38
Sexual 63 75 67 83
Fatigue 71 76 69 76
MDS-specific 67 71 56 69
Treatment outcome index 56 56 56 47