Association between treatment-emergent cytopenias and clinical responses to imetelstat in lower-risk myelodysplastic syndromes

Myelodysplastic syndromes/neoplasms (MDS) are myeloid malignancies with ineffective hematopoiesis, resulting in variable cytopenias and increased risk of progression to acute myeloid leukemia (AML) [ 1 , 2 ]. Imetelstat, a first-in-class competitive telomerase inhibitor, is an approved therapy in the US and Europe for adults with lower-risk MDS (LR-MDS) with red blood cell (RBC) transfusion-dependent (TD) anemia who are relapsed or refractory to, or ineligible for, erythropoiesis-stimulating agents (ESAs) [ 3 , 4 ]. In the Phase III IMerge trial (NCT02598661), a significantly higher proportion of patients on imetelstat achieved RBC transfusion independence (TI) than placebo [ 5 ]. The most common grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (68%) and thrombocytopenia (62%), mostly occurring within the first 3 cycles of imetelstat [ 5 ]. These events were generally transient and associated with similarly low rates of grade 3/4 clinical consequences (bleeding, infection, and febrile neutropenia) as placebo [ 5 ]. As neutropenia and thrombocytopenia occurring early with lenalidomide treatment have been correlated with clinical response in patients with del(5q) LR-MDS, suggesting an on-target, disease-modifying effect on the del(5q) clone [ 6 ], we conducted a post hoc analysis to evaluate the association between early treatment-emergent cytopenias with imetelstat and clinical responses.