Eltrombopag Reduces Bleeding, Raises Platelet Counts in Low-Risk MDS

"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," according to the authors of the phase 2 EQOL-MDS study (NCT02912208).

Eltrombopag (Promacta) appeared to be an effective and tolerable therapy vs placebo in a cohort of patients with low-risk myelodysplastic syndromes (MDS) and severe thrombocytopenia, according to long-term data from the phase 2 EQOL-MDS study (NCT02912208).

After a median follow-up of 25 weeks (interquartile range [IQR], 14-68), 42.3% of patients treated with eltrombopag (n = 112) experienced a platelet response vs 11.1% of those treated with placebo (n = 57; odds ratio, 5.9; 95% CI, 2.3-14.9; P <.001). Eltrombopag yielded complete responses (CRs) in 31 patients compared with none in the placebo arm. As of the data cutoff on March 3, 2022, 34.0% of responding patients in the eltrombopag arm remain in response; the corresponding figure in the placebo arm was 16.6%.

In total, 25.5% of responding patients lost their platelet response on eltrombopag. The rate of cumulative thrombocytopenia relapse-free survival was 63.6% (95% CI, 46.0%-81.2%) at 60 months. Clinically significant bleeding was less common with eltrombopag vs placebo (incidence rate ratio, 0.54; 95% CI, 0.38-0.75; P = .0002).

Platelet transfusion independence was achieved in 54.3% of patients receiving eltrombopag vs 35.3% receiving placebo (P = .24). The median duration of transfusion independence was 32 weeks (IQR, 14-64) and 9 weeks (IQR, 2-98), respectively (P = .15).

MDS progression occurred in 8% vs 9% of patients in the eltrombopag and placebo arms, respectively (χ2 = 0.062; P = .774). Evolution to acute myeloid leukemia occurred in 9% vs 7% of patients, respectively (χ² = 0.120; P = .729), after a median time from treatment start of 13 weeks (range, 11-24) vs 34 weeks (range, 7-133).

“The occurrence of severe thrombocytopenia in patients with low-risk MDS still represents a challenging condition because of the important burden of related adverse effects [AEs] and the lack of effective treatments. In most countries, only [platelet transfusions] are currently offered to prevent or treat bleeding in these patients. Despite this unmet clinical need, few investigational products have been tested,” the investigators wrote. “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.”

Investigators enrolled a study population of 169 patients in the single-blind, randomized, controlled EQOL-MDS trial, 165 of whom were included in the modified intention-to-treat analysis after receiving at least a single dose of the study treatment. The most common MDS-related concomitant treatments were erythropoiesis-stimulating agents (16.0%), steroids (16.0%), and deferasirox (5.9%).

Across the total enrolled population, the median age was 72 years (IQR, 65-79), and the median duration of MDS was 14 months (IQR, 4-40). Most patients (61.5%) were male (61.5%) and had low-risk disease according to the revised International Prognostic Scoring System (59.2%). Most patients were platelet (69.2%) and red blood cell (72.8%) transfusion independent at baseline.

Patients received oral eltrombopag or a matched placebo at an initial dose of 50 mg once daily. The dosage was titrated in 50-mg increments every 2 weeks up to 300 mg to produce a complete platelet response, which was defined as a platelet count of at least 100 × 103/mm³ without bleeding.

The primary end points were the duration of platelet response and long-term safety. The difference in time to response, the frequency of platelet infusions during and after treatment, and the duration of transfusion independence were among the secondary end points.

Grade 3/4 nonhematologic AEs affected 50 patients treated with eltrombopag (exposure adjusted incidence rate [EAIR], 2.5; 95% CI, 1.9-3.4) and 11 receiving placebo (EAIR, 1.6; 95% CI, 0.8-2.8). A significant difference in nonhematologic AEs between the arms (P = .002) favored placebo. Permanent treatment discontinuation was necessary for 18 patients in the eltrombopag arm after a median time from baseline of 13 weeks (IQR, 6-20) due to severe liver toxicity or persistent grade 3/4 AEs. Both arms had similar incidences of grade 1/2 AEs (P = .868).

“As expected, patients in the eltrombopag arm had a higher rate of nonhematologic AEs,” the investigators wrote. “Most grade 3/4 AEs occurred early during treatment, within the first 24 weeks, and were reversible upon drug discontinuation. However, no differences were reported between the two arms for deaths.”

Reference

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