Slide 1: Favorable Overall Survival With Imetelstat Correlates With Other Clinical Benefits in Myelofibrosis
Abstract # 53 Favorable Overall Survival With Imetelstat Treatment Correlates With Other Clinical Benefits in Intermediate 2 or High Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor John Mascarenhas, MD1, Rami S. Komrokji MD2, Michele Cavo, MD3, Bruno Martino, MD4, Dietger Niederwies
Slide 2: Disclosure
Disclosure ❑ Presenter: John Mascarenhas, MD ❑ Affiliations: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY, USA ❑ Disclosure: – Consultancy: Celgene/BMS, Incyte, Roche, PharmaEssentia, Constellation, Kartos, Prelude, Geron, Abbvie – Research funding: CTI Biopharma, Incyte, Jans
Slide 3: Background
Background ❑ Myelofibrosis (MF) is a serious and life-threatening myeloproliferative neoplasm ❑ Patients who are relapsed after or refractory to (R/R) therapy with Janus kinase inhibitors (JAKi) have dismal overall survival (OS) of 13-16 months.1,2 ❑ Imetelstat, a 13-mer oligonucleotide that specifi
Slide 4: Imetelstat: First-in-Class Telomerase Inhibitor
Imetelstat: First-in-Class Telomerase Inhibitor Imetelstat • Proprietary: 13-mer thio-phosphoramidate oligonucleotide complementary to hTR, with covalently-bound lipid tail to increase cell permeability. • Potent, first in class competitive inhibitor of telomerase: IC50 = 0.5-10 nM ❑ Short telomere
Slide 5: Dose Related Clinical Benefits with Imetelstat Treatment
Dose Related Clinical Benefits with Imetelstat Treatment 4.7 mg/kg 9.4 mg/kg Clinical Benefits (N = 48) (N = 59) Median OS, months (95% CI) 19.9 (17.1, 33.9) 28.1 (22.8, 31.6) Symptom Response at week 24 (TSS reduction ≥50%), n (%) 3 (6.3%) 19 (32.2%) Spleen Response at week 24 (SVR ≥35% by IRC), n
Slide 6: Objectives and Methods For Current Analysis
Objectives and Methods For Current Analysis Objectives: ❑ To evaluate the association between overall survival (OS) and spleen response, symptom response and fibrosis improvement. ❑ To explore the prognostic pretreatment baseline characteristic factors on OS. Methods ❑ Spleen response: spleen volume
Slide 7: Potential OS Improvement with 9.4 mg/kg Imetelstat Treatment in Patients with MF R/R to JAKi
Potential OS Improvement with 9.4 mg/kg Imetelstat Treatment in Patients with MF R/R to JAKi OS analysis was performed based on database lock in April 2020; median follow-up was 41.7 months (range 0.2, 49.2) Similar results were observed when sensitivity analyses accounted for confounding factors of
Slide 8: Lower Risk of Death Correlates with Improved Bone Marrow Fibrosis
Lower Risk of Death Significantly Correlates with Improved Bone Marrow Fibrosis in Patients Treated with Imetelstat ❑ Dose related improvement in bone marrow fibrosis ❑ Patients with improved or stable bone marrow fibrosis had lower risk of death than those who had worsening bone marrow fibrosis 4.7
Slide 9: Patients with Symptom Response Trend to Have Lower Risk of Death
Patients with Symptom Response Trend to Have Lower Risk of Death Dose-dependent symptom response: higher response rate seen in 9.4mg/kg arm than in 4.7 mg/kg arm Patients who achieved symptom response demonstrated a trend of lower risk of death compared to those who did not achieve symptom response
Slide 10: Patients with SVR Trend to Have Lower Risk of Death
Patients with SVR Trend to Have Lower Risk of Death Dose-dependent spleen volume reduction (SVR) at week 24 or at any time 4.7 mg/kg 9.4 mg/kg Patients who achieved at least >=10% SVR demonstrated Spleen volume reduction (N = 48) (N = 59) a trend of lower risk of death compared to those who did not
Slide 11: Predictive Disease Characteristics for Survival After Imetelstat Treatment
Predictive Disease Characteristics for Survival After Imetelstat Treatment Pretreatment DIPSS high risk, ECOG performance status, transfusion dependency, response to last JAKi, higher baseline neutrophils, lower baseline Hb and platelet values correlated with increased risk of death N: Patients on b
Slide 12: Conclusions
Conclusions ❑ Imetelstat showed dose-related improvement in OS in patients who are R/R to JAKi. The survival benefit observed with imetelstat was supported by the trend of correlation with other clinical benefits. – With a median follow-up of 41.7 months, the median OS was 28.1 months for the 9.4 mg
Slide 13: Phase 3 Study Design
Phase 3 Study Design Screening Treatment Period Post-Treatment Until disease progression, unacceptable toxicity, (28 days) consent withdrawal Follow-up Randomization Imetelstat 9.4 mg/kg every 21 days End of Treatment Refractory MF Post Visit Treatment Int2/High-Risk 2:1 within 30 days (N=~320) post
Slide 14: Acknowledgements
Acknowledgements The authors thank all the patients for their participation in this study and acknowledge the collaboration and commitment of all investigators and their staff