Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge.

Abstract

6566 Background: In the IMerge trial (NCT02598661) of RBC transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory to or ineligible for erythropoiesis stimulating agents, imetelstat showed significant efficacy vs placebo (PBO) for 8-wk, 24-wk, and 1-y TI endpoints, with neutropenia and thrombocytopenia as the most common adverse events (Platzbecker. Lancet 2024). Supportive care was given to all pts as needed, per investigator discretion. Here we report RBC-TI rates in the absence of platelet transfusions or myeloid growth factor use. Separately, RBC-TI with mean central hemoglobin (Hb) rise of ≥1.5 g/d was assessed in all pts. Methods: Pts were randomized 2:1 to receive imetelstat (n=118) 7.5 mg/kg or PBO (n=60) Q4W IV until disease progression. Primary endpoint was 8-wk RBC-TI; 24-wk RBC-TI was a key secondary endpoint. Primary analysis cutoff was Oct 2022, with Oct 2023 cutoff for 1-y RBC-TI analyses. Results: Overall, 21/118 (18%) pts in the imetelstat group and 1/60 (2%) pts in the PBO group needed platelet transfusions; 41/118 (35%) and 2/60 (3%) pts received myeloid growth factors, respectively. Significantly higher percentages of pts achieved 8-wk, 24-wk, and 1-y RBC-TI with imetelstat vs PBO in the absence of either platelet transfusions or growth factor support (Table). In a separate analysis, 8-wk, 24-wk, and 1-y RBC-TI and concurrent Hb rise of ≥1.5 g/dL with imetelstat vs PBO occurred in 28% vs 2%, 23% vs 0%, and 17% vs 0% of pts, respectively (Table). Among responders, imetelstat increased median central Hb levels compared with PBO: 3.6 g/dL vs 0.8 g/dL for 8-wk, 4.2 g/dL vs 1.1 g/dL for 24-wk, and 5.2 g/dL vs 1.7 g/dL for 1-y RBC-TI. Conclusions: Results from this subanalysis confirm that pts who achieve RBC-TI with imetelstat do so without developing severe neutropenia and thrombocytopenia (functionally defined as needing myeloid growth factors or platelet transfusions, respectively), therefore not negating the clinical benefit of the drug. Imetelstat also led to significant rise in Hb levels in RBC-TI responders, particularly long-term responders. These data further support the efficacy of imetelstat in TD pts with LR-MDS. Clinical trial information: NCT02598661 . [Table: see text]