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

Amer Methqal Zeidan Yale University, New Haven, CT info_outline Amer Methqal Zeidan, Valeria Santini, Uwe Platzbecker, Mikkael A. Sekeres, Michael R. Savona, Pierre Fenaux, Yazan Madanat, Azra Raza, Qi Xia, Libo Sun, Jennifer Riggs, Sheetal Shah, Shyamala Chendeal Navada, Tymara Berry, Rami S. Komrokji

Authors Amer Methqal Zeidan Yale University, New Haven, CT info_outline Amer Methqal Zeidan, Valeria Santini, Uwe Platzbecker, Mikkael A. Sekeres, Michael R. Savona, Pierre Fenaux, Yazan Madanat, Azra Raza, Qi Xia, Libo Sun, Jennifer Riggs, Sheetal Shah, Shyamala Chendeal Navada, Tymara Berry, Rami S. Komrokji Organizations Yale University, New Haven, CT, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy, Medical Clinic and Policlinic, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, Vanderbilt University Medical Center, Nashville, TN, Hôpital Saint-Louis, Université de Paris, Paris, France, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, Columbia University Medical Center, New York, NY, Geron Corporation, Parsippany, NJ, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Abstract Disclosures Research Funding Geron Corporation 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. IMerge phase 3 RBC-TI. Pts, n (%) 8-wk TIImetelstat 8-wk TI PBO 8-wk TI P value 24-wk TIImetelstat 24-wk TI PBO 24-wk TI P value 1-y TIImetelstat 1-y TI PBO 1-y TI P value RBC-TI in ITT* 47 (40) 9 (15) <.001 33 (28) 2 (3) <.001 21 (18) 1 (2) .002 RBC-TI + Mean Central Hb Increase ≥1.5 g/dL 33 (28) 1 (2) <.001 27 (23) 0 <.001 20 (17) 0 <.001 RBC-TI + Platelet TI 46 (39) 9 (15) .001 32 (27) 2 (3) <.001 19 (16) 1 (2) .004 RBC-TI + No Myeloid Growth Factors 46 (39) 9 (15) .001 32 (27) 2 (3) <.001 21 (18) 1 (2) .002 *ITT, intent-to-treat; includes pts receiving platelet transfusions and myeloid growth factors.

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