Lenalidomide and Eltrombopag for Treatment of Low- or Intermediate-Risk Myelodysplastic Syndrome: Result of a Phase II Clinical Trial

Purpose: Thrombocytopenia is a serious complication of myelo-dysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocyto-penia in MDS.Patients and Methods: We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low-or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or throm-bocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.Results: Fifty-two patients were enrolled; mean age was 71 years (range 34-93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Pl atelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematologic grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.Conclusions: ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/ intermediate-risk MDS.

Automated summary

The study aimed to evaluate the therapeutic effect of Eltrombopag and Lenalidomide in patients with low-risk or intermediate-risk myelo-dysplastic syndromes (MDS). The results showed that both ELT and LEN monotherapy, as well as combination therapy, can improve hematologic parameters in patients and are well tolerated.