C052 | OUTCOMES OF IMETELSTAT THERAPY IN PATIENTS WITH RING SIDEROBLAST–NEGATIVE LOWER-RISK MYELODYSPLASTIC SYNDROMES FROM THE POOLED IMERGE STUDY POPULATIONS

The majority of LR-MDS are in the heterogenous group of RS− disease. Current treatment (tx) options are limited in number and efficacy, particularly for pts who are relapsed or refractory (R/R) to or ineligible for erythropoiesis-stimulating agents (ESA). First-line luspatercept (LUS) demonstrated differential efficacy in RS+ vs RS− disease; LUS also showed benefit vs. placebo (PBO) in second-line tx for RS+ disease. Imetelstat (IME) is a first-in-class, direct, and competitive inhibitor of telomerase activity approved for the tx of adult pts with LR-MDS with transfusion-dependent anemia who are R/R to or ineligible for ESAs based on the results of the IMerge trial (NCT02598661). In the RS− LR-MDS subpopulation of the Phase 3 of IMerge (IME, n=44; PBO, n=23), more pts on IME vs PBO (32% vs 9% [P=.038] and 20% vs 0% [P=.019]) achieved ≥8-wk and ≥24-wk red blood cell transfusion independence (RBC-TI), respectively. This post hoc analysis evaluated outcomes in pts with RS− LR-MDS pooled from the 3 parts of IMerge (Phase 2, 3, and QTc substudy) who received IME 7.1 mg/kg active dose (7.5 mg/kg IME sodium) or PBO via 2-h IV infusion every 4 wk. At data cutoff dates (Phase 2/3, 10/13/2023; QTc substudy, 10/13/2024), 78 IME-treated pts had RS− disease (median [range]: 26 mo [1-87] on-study follow-up). Baseline characteristics were similar to the Phase 3 overall population: median baseline transfusion burden of 6.5 U/8 wk, median time from initial diagnosis of 2.8 y, 51% had serum erythropoietin ≤500 mU/mL, and 79% and 6% had prior ESA and LUS, respectively. Of these pts, 33% achieved ≥8-wk RBC-TI (median duration of response [mDOR],44 wk), 21% achieved ≥24-wk RBC-TI (mDOR,123 wk), and 13% achieved ≥1-y RBC-TI (mDOR,141 wk). Hematologic improvement-erythroid (HI-E) per International Working Group (IWG) 2006 showed transfusion reduction ≥4 U/8 wk and hemoglobin (Hb) rise ≥1.5 g/dL lasting ≥8 wk in 55% and 24% of pts, respectively. Per HI-E IWG 2018, 11 and 67 pts had low transfusion burden [LTB] and high transfusion burden [HTB], respectively. 36% of LTB pts achieved an HI-E response (16-wk RBC-TI). 22% and 40% of HTB pts achieved major (16-wk RBC-TI) and minor (50% RBC transfusion reduction/16 wk) HI-E responses, respectively. Taken together, results from this post hoc analysis align with prior findings and further support that IME has clinical activity in pts with difficult-to-treat RS− disease with a HTB, and with different clinical MDS subtypes with no available tx options.