Effect of prior treatment (tx) on the clinical activity of imetelstat (IME) in transfusion-dependent (TD) patients (pts) with erythropoiesis-stimulating agent (ESA), relapsed or refractory (R/R)/ineligible lower-risk myelodysplastic syndromes (LR-MDS

6569 Background: IME, a first-in-class, direct, and competitive inhibitor of telomerase activity, was approved in the US for the tx of red blood cell (RBC)-TD LR-MDS in pts who are R/R or ineligible for ESA based on the results of the pivotal IMerge trial (NCT02598661). IMerge demonstrated significant and durable efficacy of IME (n=118) versus placebo (n=60) for ≥8-week, ≥24-week, and ≥1-year RBC-transfusion independence (TI), with a generally manageable safety profile in this pt population. Here, we pooled data from the 3 parts of the IMerge trial (phase 2, phase 3, and QTc substudy) to investigate the effect of prior txs on the clinical activity of IME. Methods: In IMerge, pts received IME intravenously every 4 weeks at 7.1 mg/kg active dose (7.5 mg/kg IME sodium equivalent). Prior lenalidomide (LEN) and prior hypomethylating agent (HMA) use were exclusion criteria in phase 3 only. In this analysis, pooled data from IME-treated pts (phase 2, phase 3, and QTc substudy) were analyzed by prior tx: ± ESA, luspatercept (LUSP), LEN, and HMA; pts may have received >1 prior tx. Outcomes included ≥8-week, ≥24-week, and ≥1-year RBC-TI, rates of hematologic improvement-erythroid (HI-E) based on the revised International Working Group (IWG) 2018 criteria, transfusion reduction of ≥4 U/8 weeks, and a hemoglobin (Hb) rise of ≥1.5 g/dL for ≥8 weeks. Results: The data cutoff dates were 10/13/2023 (phase 2/3) and 10/13/2024 (QTc substudy). A total of 226 IME-treated pts pooled in IMerge were included in this analysis; most pts (n=188) had a high transfusion burden (TB) per revised IWG 2018 at baseline (vs low TB [n=38]; Table). Of all pts, 39% achieved ≥8-week RBC-TI (median duration of response, 55 weeks), and 28% and 18% achieved ≥24-week and ≥1-year RBC-TI, respectively. Among all IME-treated pts, 204 had prior tx with an ESA and 22 were ineligible for ESAs; 36 had prior LUSP, 26 had prior LEN, and 22 had prior HMA. Pt characteristics and efficacy by prior tx are shown in the table. Conclusions: Pts who were ESA ineligible or who had prior tx with LUSP, LEN, or HMA, and were largely high TB, in IMerge experienced clinical benefit from IME tx, though the number of pts was small. Given the limited efficacy data available in later lines of tx for LR-MDS, these results have important clinical implications, suggesting that IME has clinical activity regardless of prior txs. Clinical trial information: NCT02598661 . ESA ineligible(n=22) Prior ESA(n=204) Prior LUSP(n=36) Prior LEN(n=26) Prior HMA(n=22) TB at baseline, nLow TBHigh TB 319 35169 531 422 319 ≤8-week RBC-TI, %Median duration of RBC-TI for ≥8-week TI responders, weeks 3632 4060 3170 2341 1441 ≥24-week RBC-TI, % 14 29 22 19 9 ≥1-year RBC-TI, % 9 19 14 8 0 HI-E (IWG 2018), % 41 44 31 35 23 Transfusion reduction of ≥4 U/8 weeks (IWG 2006), % 64 64 69 54 50 Hb rise ≥1.5 g/dL for ≥8 weeks (IWG 2006), % 27 34 31 19 14