Lower risk MDS are characterised by a relatively low risk of progression to acute myeloid leukaemia (AML), but by chronic and debilitating anaemia, that responds inconstantly and transiently to ESAs (including EPO and darpbepoietin), requiring after ESA failure regular red blood cell (RBC) transfusions, with poor quality of life.
Limited options are possible in those patients to avoid transfusions.
Higher telomerase activity and shorter telomeres predict for shorter overall survival in lower risk MDS.
Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomere length and active telomerase, which has shown clinical activity in myeloid malignancies (especially primary myelofibrosis).
In the present trial, 38 lower risk (non del 5q) patients resistant to ESA (and having received no hypomethylating agents or lenalidomide, drugs not approved in this situation in Europe), with a high transfusion requirement (median 8 RBC units transfused/ 8 weeks) received imetelstat (7.5 mg/kg) for a median of 9 cycles.
16 (42%) achieved transfusion independence (TI), for a median actuarial duration of 86 weeks.
The results of the study were presented at the 2019 European Hematology Association (EHA) Annual Meeting.
Side effects included reversible neutropenia and thrombocytopenia in about 60% of the patients.
This places imetelstat as a very interesting second line treatment of anaemia of lower risk MDS after ESA failure.
A phase III trial comparing imeltelstat and placebo in this situation will start soon.