Rytelo (imetelstat) / Geron - LARVOL DELTA

Imetelstat for low and intermediate risk myelodysplastic syndromes without 5q deletion in transfusion-dependant patients (PubMed, Bull Cancer) - No abstract available

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Individualizing Treatment Selection in MF (SOHO 2025) - P3 | "These include the activin receptor ligand trap luspatercept, the telomerase inhibitor imetelstat, the selective inhibitor of nuclear export selinexor, the human double minute 2 inhibitor navtemadlin, and the bromodomain and extra-terminal protein inhibitor pelabresib...Elritercept — another activin receptor ligand trap — and the anti-hemojuvelin antibody DISC-0974 are being developed for anemia of MF...Currently, these patients are observed or managed for thrombotic risk similarly to those with essential thrombocythemia (ET) — receiving hydroxyurea for control of cytoses, ruxolitinib for symptoms, or interferon for long-term disease modification. Encouraging data on ruxolitinib in patients with intermediate-1-risk MF, along with analyses from the COMFORT trials demonstrating the benefits of early initiation of ruxolitinib in patients with intermediate-2/high-risk MF and intriguing evidence of event-free survival (EFS) improvement with both ruxolitinib and..."

Clinical • Essential Thrombocythemia • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Non-melanoma Skin Cancer • Oncology • Polycythemia Vera • Skin Cancer • Solid Tumor • ACVR1 • IRAK1

Beyond Hypomethylating Agents: Novel Therapies and Targeted Approaches. (PubMed, Clin Hematol Int) - "While early excitement was significant, clinical trials of the immune checkpoint inhibitors (ICIs) ipilimumab and durvalumab have produced no definitive results, highlighting the need for better patient selection and combination regimens. Emerging drugs luspatercept and imetelstat have been suggested for lower-risk MDS (LR-MDS) by promoting transfusion independence and global hematologic response. In contrast, exploratory agents such as pevonedistat, magrolimab, and sabatolimab are under further investigation for HR-MDS...Identification of predictive biomarkers for response to targeted therapies and immunotherapies is crucial to optimize patient outcomes. An integrated, patient-centered approach combining genomics, novel therapeutics, and immunomodulation is therefore essential to address the current needs in MDS management."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology

Is Combination Therapy Here for MPN? (SOHO 2025) - "2 Outside of the potential benefit of type 2 (AJ1-11095) and JAK2 V617F-selective (INCB160058) inhibitors under phase 1 evaluation, the research community has focused efforts on developing rational JAK inhibitor-based combination therapy regimens...3 Data from prospective and retrospective studies suggest a correlation between spleen reduction and OS with ruxolitinib and pacritinib...Nevertheless, the combination of pelabresib and ruxolitinib was well tolerated, and biomarkers of disease modification — including reduction in bone marrow fibrosis, driver mutation allele frequency, and inflammatory cytokine expression levels — all favored the combination, supporting the proposed mechanism of action and published preclinical synergy...11 The phase 3 trial will aim to confirm this activity in patients who have received at least 18 weeks of ruxolitinib therapy and meet rigorously defined criteria for suboptimal response, after which these patients will be randomized to..."

Combination therapy • IO biomarker • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD34 • XPO1

Outcomes of Imetelstat Therapy in Patients With Ring Sideroblast-Negative (RS-) Lower-Risk Myelodysplastic Syndromes (LR-MDS) From the Pooled IMerge Study Populations (SOHO 2025) - P2/3 | "Baseline characteristics were similar to the phase 3 population: median baseline transfusion burden of 6.5 U/8 weeks, median of 2.8 years from initial diagnosis, 51% with serum erythropoietin ≤500 mU/mL, and 79% and 6% with prior ESA and luspatercept treatment, respectively. Results from this post hoc analysis align with prior findings and support the use of imetelstat in patients with ESA R/R/ ineligible, RS- LR-MDS for whom there are currently no FDA-approved therapies. Funding: Geron Corporation."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Advances and Challenges in the Management of Myelodysplastic Syndromes. (PubMed, Cancers (Basel)) - "For lower-risk MDS, the treatment paradigm has evolved beyond erythropoiesis-stimulating agents (ESAs) with the introduction of novel effective agents such as luspatercept and imetelstat, as well as shortened schedules of hypomethylating agents (HMAs). This review provides a comprehensive overview of the current treatment approach for MDS, highlighting new classifications, prognostic tools, evolving therapeutic options, and ongoing challenges. We discuss evidence-based recommendations, treatment sequencing, and emerging clinical trials, with a focus on translating biological insights into improved outcomes for patients with MDS."

Journal • Review • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Survival Benefit and Resource Utilization of First-Line Treatment With Luspatercept vs First-Line Erythropoiesis-Stimulating Agents for Lower-Risk Myelodysplastic Syndromes: Results of Model Simulation (SOHO 2025) - P2/3, P3 | "First-line (1L) treatments for anemia include luspatercept and erythropoiesis-stimulating agents (ESAs); second-line (2L) treatments include luspatercept, imetelstat, ESAs, and best supportive care (BSC). This analysis indicates that 1L luspatercept treatment is associated with longer patient survival, gain in QALYs, and lower transfusion and HCRU burden compared with 1L ESA, regardless of 2L treatment choice."

Clinical • HEOR • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Imetelstat: A First-in-Class Telomerase Inhibitor for the Treatment of Patients With Lower-Risk Myelodysplastic Syndromes and Anemia. (PubMed, J Adv Pract Oncol) - "Grade 3 to 4 hematologic events occurred early in the treatment and had a median duration of 1.9 weeks for neutropenia and 1.4 weeks for thrombocytopenia; cases resolved to grade ≤ 2 within 2 weeks in 81% and 86% of cases, respectively, with limited severe complications. This review highlights key topics related to the use of imetelstat in patients with LR-MDS, including its mechanism of action, clinical efficacy and safety data, dosing and administration, management of adverse events, and notable clinical practice implications."

Journal • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Outcomes With Imetelstat by Serum Erythropoietin (sEPO) Levels in Patients With Lower-Risk Myelodysplastic Syndromes (LR-MDS) Who Were Treatment Naive or Who Had Prior Treatment With Erythropoiesis-Stimulating Agents (ESAs) (SOHO 2025) - P2/3 | "In this post hoc pooled analysis, treatment-naive patients with LR-MDS and high baseline sEPO, as well as patients who were relapsed or refractory to ESA treatment (regardless of baseline sEPO levels) experienced clinical benefit with imetelstat treatment, supporting its use in these settings. Funding: Geron Corporation."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

IMpactMF, Randomized, Open-Label, Phase 3 Trial of Imetelstat Versus Best Available Therapy (BAT) in Patients With Intermediate-2 (INT-2) or High-Risk (HR) Myelofibrosis Relapsed or Refractory (R/ R) to Janus Kinase Inhibitors (JAKi) (SOHO 2025) - P2, P3 | "As of February 2025, 172 sites in North and South America, Europe, the Middle East, Australia, and Asia have enrolled ≈80% of patients. The planned interim analysis (when ≈35% of patients planned to be enrolled have died) is expected in the second half of 2026. Funding: Geron Corporation."

Clinical • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Geron Corporation Reports Second Quarter 2025 Financial Results and Recent Business Highlights (Geron Corporation Press Release) - "Achieved $49.0 million in RYTELO net product revenue in Q2 2025....IMpactMF Phase 3 Clinical Trial Evaluating imetelstat in relapsed/refractory myelofibrosis: Reached over 95% enrollment as of end of July, with full enrollment expected by year-end 2025. Interim analysis readout for overall survival expected in the second half of 2026 (when approximately 35% of patient events have occurred), and final analysis expected in the second half of 2028 (when approximately 50% of patient events have occurred)."

P3 data • Sales • Myelodysplastic Syndrome • Myelofibrosis

Management of Anemia in Lower-Risk Myelodysplastic Syndromes/Neoplasms With Novel Agents. (PubMed, JCO Oncol Pract) - "Novel insights in the pathogenesis of MDS and results from positive phase III clinical trials in LR-MDS have led to a growing number of therapeutic options (eg, luspatercept and imetelstat). Imetelstat was recently added as a new agent for patients who are refractory/resistant or ineligible for erythropoiesis-stimulating agent treatment on the basis of the randomized phase III IMerge trial, showing that imetelstat led to the primary end point of RBC-TI for ≥8 weeks in 40% of patients compared with 15% in patients receiving placebo. However, future clinical trials are needed to investigate the optimal sequencing of different agents and the potential of improving efficacy using combination of therapeutic strategies in LR-MDS."

Journal • Review • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

IMPROVEMF UPDATE: PHASE 1/1B TRIAL OF IMETELSTAT (IME)+RUXOLITINIB (RUX) IN PATIENTS WITH INTERMEDIATE (INT)-1, INT-2, OR HIGH-RISK (HR) MYELOFIBROSIS (MF) (EHA 2025) - P1, P2 | "In part 1 of IMproveMF, no DLTs were observed and the RP2D dose of 9.4 mg/kg IME was determined. AEs were consistent with those observed in other IME clinical trials, and preliminary efficacy was positive, demonstrating the potential of IME+RUX in this pt population with high unmet needs. Part 2 of this trial is ongoing across the United States at 6 sites."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Infectious Disease • Leukopenia • Myelofibrosis • Neutropenia • Pain • Pneumonia • Respiratory Diseases

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN MYELODYSPLASTIC SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Newer agents included Rigosertib (41%, n=312/770), Imetelstat (15%, n=118/770), Pembrolizumab (8%, n=65/770), Enasidenib (9%, n=67/770), and Sabatolimab (7%, n=53/770) Ivosidenib (6%, 45/770), Elritercept 2%, n=15 /770), Pevonedistat (3%, 21/770), Emavusertib (2%, 15/770), Atezolizumab (6%, 46/770), and Olutasidenib (2%, n=13/770). The most commonly used conventional agent was azacitidine (19%, n= 147/770)... This study highlights promising results with the investigational agents for MDS. However, large studies with more power are needed to strengthen our understanding of these investigational agents in MDS patients."

Combination therapy • Monotherapy • Retrospective data • Review • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Advances and challenges in the treatment of myelodysplastic syndromes. (PubMed, Exp Hematol Oncol) - "Only the hypomethylating agents (HMA) lenalidomide and imetelstat reduced the mutational burden, and then only in a small subset of cases. Here we summarize the current standard therapeutic approaches for MDS patients and discuss major advances in MDS research and treatments. We also discuss major challenges and potential solutions to overcome these challenges for future MDS research and drug development."

Journal • Review • Tumor mutational burden • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • TMB

CHARACTERIZATION AND MANAGEMENT OF TRANSIENT CYTOPENIAS ASSOCIATED WITH IMETELSTAT (IME) IN LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS) FROM THE IMERGE TRIAL (EHA 2025) - P2/3 | "In this post-hoc analysis of pooled IME-treated pts from the IMerge study, grade 3/4 neutropenia and thrombocytopenia events largely occurred early in treatment, had a short duration, and did not lead to any significant clinical consequences. Neutropenia and thrombocytopenia with IME treatment were generally manageable with cycle delays and dose reductions and did not lead to treatment discontinuation in most pts. Sponsor: Geron Corporation."

Acute Myelogenous Leukemia • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

TRIAL IN PROGRESS: MIDAS - A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF MOMELOTINIB IN PATIENTS WITH ANEMIA DUE TO LOWER-RISK MYELODYSPLASTIC SYNDROMES (EHA 2025) - P2 | "First-line treatments include erythropoiesis-stimulating agents (ESAs) or luspatercept, and imetelstat is a second-line option following ESAs...Patients may enroll regardless of ring sideroblast status, while those with del5q cytogenetic abnormalities are ineligible regardless of prior lenalidomide exposure.In part 1 (Figure), 40 patients will be stratified by baseline transfusion burden (≤6 vs >6 units in 8 weeks) and randomized 1:1 to 1 of 2 momelotinib dose levels to establish the RP2D, at which up to 40 patients will be enrolled in part 2... This will be the first clinical study of momelotinib in patients with LR-MDS and anemia. Part 1 enrollment is planned to begin in April 2025."

Clinical • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • IRAK1 • JAK1 • JAK2

OUTCOMES WITH IMETELSTAT BY SERUM ERYTHROPOIETIN LEVELS IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO WERE TREATMENT NAIVE OR WHO HAD PRIOR TREATMENT WITH ERYTHROPOIESIS-STIMULATING AGENTS (EHA 2025) - P2/3 | "In this post hoc pooled analysis, patients with LR-MDS who were treatment naive and had high sEPO at baseline experienced clinical benefit with imetelstat. Additionally, patients who had prior ESA therapy experienced clinical benefit with imetelstat regardless of baseline sEPO levels, including those with sEPO >500 mU/mL. Together, these findings support the use of imetelstat in the frontline setting in patients with LR-MDS who are ineligible for ESAs, and further support use in these patients after ESA therapy regardless of baseline sEPO."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

OUTCOMES OF IMETELSTAT THERAPY IN PATIENTS WITH RING SIDEROBLAST–NEGATIVE LOWER-RISK MYELODYSPLASTIC SYNDROMES FROM THE POOLED IMERGE STUDY POPULATIONS (EHA 2025) - P2/3 | "Current treatment options are limited in number and efficacy, particularly for patients (pts) who are either ineligible for erythropoiesis-stimulating agents (ESAs) or whose disease is relapsed or refractory to ESAs.First-line luspatercept demonstrated differential efficacy in RS positive compared with RS-neg disease; a benefit in RS positive disease was also observed with luspatercept in the second line compared with placebo (PBO). In this post hoc analysis, pts with RS-neg LR-MDS who were relapsed or refractory to or ineligible for ESAs experienced clinical benefit from IME treatment. These results were consistent with prior findings and further support that IME has clinical activity in pts with difficult-to-treat RS-neg disease with a high transfusion burden, and with different clinical subtypes of MDS with no available therapy options. Sponsor: Geron Corporation."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH IMETELSTAT IN THE IMERGE TRIAL (EHA 2025) - P2/3 | "In this post hoc analysis, IME-treated pts appeared to experience sustained meaningful improvements across QUALMS domains. Improvements in the physical burden domain were observed in more pts treated with IME versus PBO. A significantly higher proportion of TI responders experienced sustained meaningful improvement in QUALMS-P scores than non-responders in the IME group."

Clinical • HEOR • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Pulmonary Disease

IMPACTMF, RANDOMIZED, OPEN-LABEL, PHASE 3 TRIAL OF IMETELSTAT VERSUS BEST AVAILABLE THERAPY IN PATIENTS WITH INTERMEDIATE-2 OR HIGH-RISK MYELOFIBROSIS RELAPSED OR REFRACTORY TO JANUS KINASE INHIBITORS (EHA 2025) - P2, P3 | "Randomization is to IME sodium 9.4 mg/kg (8.9 mg/kg active dose) intravenously q3w or investigator-selected best available therapy (BAT; eg, hypomethylating agents, hydroxyurea, interferon, thalidomide, danazol, chemotherapy, or other non–JAKi-containing therapy, but not hematopoietic stem cell transplantation or splenectomy). Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting."

Clinical • P3 data • Anemia • Bone Marrow Transplantation • Cardiovascular • Fibrosis • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Myelodysplastic Syndrome • Myelofibrosis • Neutropenia • Thrombocytopenia

INCREASED DURATION OF TIME WITHOUT TRANSFUSION RELIANCE FOR PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH IMETELSTAT VERSUS PLACEBO IN THE IMERGE TRIAL (EHA 2025) - P2/3 | "This post hoc TWiTR analysis showed that patients with LR-MDS in the IME arm had a longer duration of time without transfusion reliance or relapse compared with PBO. Thus, the ability of IME to lessen TD was clinically meaningful to patients, given the negative association between TD and QOL. Sponsor: Geron Corporation."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Efficacy and safety of imetelstat in transfusion-dependent lower-risk myelodysplastic syndromes: A systematic review and meta-analysis. (ASCO 2025) - "This meta-analysis provides evidence for the efficacy of imetelstat in achieving transfusion independence in heavily transfused patients with LR-MDS and limited treatment options. Further studies are needed to confirm its efficacy and safety."

Retrospective data • Review • Acute Myelogenous Leukemia • Anemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Outcomes with imetelstat in myelofibrosis: A systematic review and meta-analysis. (ASCO 2025) - "This meta-analysis shows good efficacy of Imetelstat in MF patients with an acceptable safety profile. However, results should be interpreted cautiously considering the small sample size and large clinical trials are needed to consolidate these findings."

Retrospective data • Review • Anemia • Essential Thrombocythemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Polycythemia Vera • Thrombocytopenia • Thrombocytosis • CALR • JAK2

IMproveMF update: Phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF). (ASCO 2025) - P1, P2 | "In part 1 of IMproveMF, no DLTs were observed and the RP2D dose of 9.4 mg/kg IME was determined. AEs were consistent with those observed in other IME clinical trials, and preliminary efficacy was positive, demonstrating the potential of IME+RUX in this pt population with high unmet needs. Part 2 of this trial is ongoing across the US at 6 sites."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Infectious Disease • Leukopenia • Myelofibrosis • Neutropenia • Pain • Pneumonia • Respiratory Diseases