Eltrombopag/eltrombopag clinical trial results

A study shows that the combination treatment of eltrombopag/eltrombopag and lenalidomide is effective and safe in some patients with myelodysplastic syndrome (MDS). Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) that has been shown to be effective in increasing platelet counts in patients with MDS. Preclinical data also demonstrate that eltrombopag can reverse the anti-megakaryopoietic effects of lenalidomide in MDS patient samples.

Lenalidomide is a U.S. Food and Drug Administration (FDA)-approved therapy for the treatment of patients with del5q and has been shown to induce disease remission and transfusion independence in nearly 65% of the population. For patients with MDS without del5q, lenalidomide appears to reduce the need for transfusions in a quarter of the population, but its use is limited by the risk of severe thrombocytopenia. In addition, patients with platelet counts <50 × 109/L have traditionally been excluded from clinical trials.

The study was designed to evaluate the safety and efficacy of the combination of eltrombopag and lenalidomide in patients with low- to moderate-risk MDS (IPSS-R) or nonproliferative chronic myelomonocytic leukemia (CMML). Researchers recruited 44 patients 18 years and older with symptomatic anemia who had no prior exposure to lenalidomide or eltrombopag. Of the 44 evaluable participants (out of 51), the majority were male (70%), the median age was 71 years, 95% had MDS and 5% had CMML. 55% of IPSS-R scores were low-risk MDS. Two-thirds of the patients were untreated, and 16 patients (36%) received one or more treatment regimens, including erythropoiesis-stimulating agents.

Patients were treated based on platelet count at baseline:Arm A included patients with platelet counts ≥50 × 109/L who received 10 mg of lenalidomide daily alone on days 1 through 21 of each 28-day treatment cycle. If the platelet count fell below 50 × 10/L, lenalidomide was discontinued and eltrombopag was administered on days 1 to 28 until platelet levels exceeded 50 × 10/L for two weeks; at that time, the patient resumed lenalidomide. If the platelet count drops below 50 × 109/L again, the patient receives eltrombopag on the same schedule and concurrently with lenalidomide. In Group B, patients with platelet counts ≤50×109/L received eltrombopag from day 1 to day 28 until the platelet count reached ≥50×109/L, and then received the same treatment as patients in Group A.

The combination of eltrombopag and lenalidomide was well tolerated, with few non-hematologicalGrade 3-4 treatment-related adverse events (AEs). These AEs included Grade 3 hyperbilirubinemia (7%), Grade 3 transaminasitis (2%), Grade 3 diarrhea (2%), and Grade 3 arthralgia (2%). Two patients experienced major bleeding events and two patients died (attributed to pneumonia and gallbladder cancer). Among 31 patients treated with eltrombopag, one patient experienced a reversible increase in peripheral blood cells during treatment, and one patient developed myelofibrosis six years after treatment.

In terms of efficacy, the objective response rate (ORR) in the intention-to-treat population (n=51) was 35% (32% in Group A and 39% in Group B). A total of 13 (30%) patients achieved red blood cell transfusion independence (RBC-TI). Among 17 patients who received eltrombopag alone, the ORR was 41% (n=7/17), with 29% achieving a bile secretory response. For comparison, in 13 patients who received lenalidomide alone, the ORR was 46% (n=6/13), and all patients achieved RBC-TI. When looking at the combination of eltrombopag and lenalidomide, the ORR was 36%, with two patients achieving bile secretory remission and two patients achieving complete remission.

Lenalidomide treatment shows good efficacy in evaluable low/intermediate risk MDS patients, with an ORR of 40.9%, durable response, and acceptable safety. Eltrombopag produced single-dose responses with an acceptable safety profile and a significant proportion of multilineage responses.