Eltrombopag Demonstrated Efficacy, Relative Safety Among Patients With Low-Risk MDS and Severe Thrombocytopenia

Results from the Phase 2 EQOL-MDS Trial

According to the phase 2 EQOL-MDS trial published in the Journal of Clinical Oncology, eltrombopag, a thrombopoietin (TPO) receptor agonist, demonstrated efficacy and relative safety among patients with low-risk myelodysplastic syndromes (MDS) and severe thrombocytopenia.

“In higher-risk MDS, the addition of eltrombopag to azacitidine resulted in worse [platelet] recovery and increased progression to [acute myeloid leukemia],” stated Esther Natalie Oliva, MD, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy, and coauthors. The phase 2 EQOL-MDS trial aimed to assess the second-part long-term efficacy and safety of the treatment among patients with lower-risk MDS and severe thrombocytopenia. 

The primary end point was the duration of platelet response (PLT-R) and long-term safety and tolerability. Secondary end points included bleeding incidence, platelet transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival, and pharmacokinetics. 

This trial screened 325 patients with lower-risk or intermediate-risk MDS (according to the International Prognostic Scoring System), severe thrombocytopenia, and a stable platelet count (<30 × 103/mm3). Among these patients, 169 were randomly assigned either oral eltrombopag (n = 112) or placebo (n = 57) at a starting dose of 50 mg once daily, up to a maximum of 300 mg. 
 
In the eltrombopag group, PLT-R with 25-week follow-up was observed in 42.3% of patients (n = 47), compared to 11.1% (n = 6) in the placebo group (95% confidence interval [CI]). Among the eltrombopag group, 25.5% (n = 12) lost platelet response, with cumulative thrombocytopenia relapse-free survival at 60 months of 63.6%. Clinically significant bleeding, which was defined as a World Health Organization (WHO) bleeding score ≥ 2, occurred less frequently in the eltrombopag arm than in the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). 

While there was no significant difference in the amount of grade 1 to 2 adverse events between the groups, a higher proportion of patients who received eltrombopag exhibited grade 3 to 4 adverse events. The occurrence of acute myeloid leukemia evolution and/or disease progression was comparable between groups, with no significant differences in survival times. 

Dr Oliva et al concluded, “eltrombopag has an acceptable toxicity profile and is effective in raising and maintaining [platelet] count and reducing bleeding without any associated risk of MDS progression.”

“Administration of eltrombopag results in durable improvements in [platelet] counts in patients with low-risk MDS and appears to be well-tolerated with acceptable toxicities to date. Longer-term follow-up of the trial cohort will be important,” added Journal of Clinical Oncology Associate Editor Charles F Craddock, MD.

Source: 

Oliva EN, Riva M, Niscola P, et al. Eltrombopag for low-risk myelodysplastic syndromes with thrombocytopenia: interim results of a phase-II, randomized, placebo-controlled clinical trial (EQOL-MDS). J Clin Oncol. Published online June 9, 2023. doi:10.1200/jco.22.02699