https://ash.confex.com/ash/2015/webprogram/Paper79009.html

55 Telomerase Inhibitor Imetelstat Therapy in Refractory Anemia with Ring Sideroblasts with or without Thrombocytosis

Myeloproliferative Syndromes: Clinical
Program: Oral and Poster Abstracts
Type: Oral
Session: 634. Myeloproliferative Syndromes: Clinical: Early and Late Stage Trials in MPN
Saturday, December 5, 2015: 9:30 AM
W224, Level 2 (Orange County Convention Center)
Ayalew Tefferi, MD1, Aref Al-Kali, MD1, Kebede H. Begna, MD2, Mrinal M Patnaik, MBBS1, Terra L. Lasho, PhD1*, Xiaolin Wang, ScD3*, Ying Wan, PhD4* and Curtis A. Hanson, MD5

1Division of Hematology, Mayo Clinic, Rochester, MN
2Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
3Geron Corporation, Menlo Park, CA
4Janssen Research & Development, Raritan, NJ
5Division of Hematopathology, Mayo Clinic, Rochester, MN

Background
Imetelstat is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase reverse transcriptase. A pilot study of imetelstat therapy in myelofibrosis showed the induction of complete (CR) or partial remissions, as well as molecular remissions, in a subset of patients (Blood. 2014;124:634). In the particular study, CR was significantly higher in patients with SF3B1 or U2AF1 spliceosome mutations, which provided the rationale for the current study; spliceosome mutations are closely associated with refractory anemia with ring sideroblasts with (RARS-T) or without (RARS) thrombocytosis (Leukemia. 2013;27:1826).

Methods

Diagnosis of RARS and RARS-T was according to WHO criteria (Blood. 2009;114:937). Study patients were treated with a 2-hour intravenous infusion of 7.5 mg/kg imetelstat (Janssen Biotech Inc., Horsham, PA, USA) every 4 weeks. Drug activity was monitored by both formal response criteria (Blood. 2006;108:419) and effect on spleen size, thrombocytosis and leukocytosis. Adverse events (AEs) were monitored by Common Terminology Criteria for Advers Less

Conclusions

Treatment with imetelstat may offer clinical benefit in patients with RARS or RARS-T with generally acceptable safety profile and warrants further clinical investigation