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).
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".