(ChemotherapyAdvisor) – Ezatiostat, a glutathioneS-transferase P1-1 inhibitor that promotes the maturation of hematopoieticprogenitors and induces apoptosis in cancer cells, is well tolerated and active when used in combination with lenalidomide to treat myelodysplastic syndrome (MDS), according to a team of researchers from several U.S.-based research institutions. This conclusion is based on a paper entitled “Phase 1 Dose-ranging Study of Ezatiostat Hydrochloride in Combination with Lenalidomidein Patients with Non-deletion (5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome(MDS),” which was published online in the journal of Hematology & Oncology on April 30.
In this Phase 1 study, 19 patients with non-deletion (5q) MDS received 1 of 2 doses (2,000mg or 2,500mg per day) of ezatiostat in combinationwith 10mg of lenalidomide on days 1–21 of a 28-day cycle. Following administration, the investigators monitored patients for adverse events (AEs) and reported no unexpected toxicities, with an incidence and severity of adverse events (AEs) that were consistent with that expected for each drug in monotherapy.
Reported non-hematologic AEs in the ezatiostat-lenalidomide group were mostly grade 1 and 2 fatigue, anorexia, nausea, diarrhea, and vomiting, whereas lenalidomide-related hematologic AEs were thrombocytopenia, neutropenia, and anemia. Hematologic improvement was observed in both dosage groups: 25% of 2,500/10mg, erythroid improvement [HI-E]; 40% of 2,000mg/10mg,HI-E response. Other improvements were observed: 43% of red blood cell (RBC) transfusion-dependent patients became RBC transfusion independent; 60% of thrombocytopenicpatients had an HI-platelet (HI-P) response; 60% experienced HI-E and HI-P; 33% experienced HI-E and HI-N; and more,” the investigators wrote.
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The investigators concluded: “The tolerability and activity profile of ezatiostat co-administered with lenalidomide supports the further development ofezatiostat in combination with lenalidomide in MDS….”
