A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis

• Published in: The New England journal of medicine Vol. 373; no. 10; pp. 908 - 919
• Main Authors: Tefferi, Ayalew, Lasho, Terra L, Begna, Kebede H, Patnaik, Mrinal M, Zblewski, Darci L, Finke, Christy M, Laborde, Rebecca R, Wassie, Emnet, Schimek, Lauren, Hanson, Curtis A, Gangat, Naseema, Wang, Xiaolin, Pardanani, Animesh
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 03-09-2015
• Subjects: Aged; Alkaline phosphatase; Aspartate aminotransferase; Bilirubin; Body weight; Bone cancer; Bone marrow; Bone Marrow Cells - drug effects; Bone Marrow Cells - pathology; Cell division; DNA Mutational Analysis; Drug Administration Schedule; Drug dosages; Female; Fibrosis; Fibrosis - drug therapy; Humans; Indoles - administration & dosage; Indoles - adverse effects; Infusions, Intravenous; Inhibitor drugs; Intravenous administration; Janus kinase; Janus kinase 2; Janus Kinase 2 - genetics; Kinases; Male; Middle Aged; Mutation; Myelofibrosis; Myelosuppression; Neutropenia; Niacinamide - administration & dosage; Niacinamide - adverse effects; Niacinamide - analogs & derivatives; Oligonucleotides; Patients; Pilot Projects; Polycythemia Vera - complications; Primary Myelofibrosis - drug therapy; Primary Myelofibrosis - etiology; Primary Myelofibrosis - genetics; Remission; Remission Induction; Ribonucleic acid; RNA; RNA-directed DNA polymerase; Spleen; Telomerase; Telomerase - antagonists & inhibitors; Telomerase inhibitors; Telomerase reverse transcriptase; Thrombocythemia, Essential - complications; Thrombocytopenia; Transaminases - drug effects
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1310523

Imetelstat, a telomerase inhibitor, induced complete or partial responses in 21% of patients with refractory myelofibrosis. In some patients, reversal of marrow fibrosis was documented and the burden of mutant clones decreased. Myelosuppression was the key toxic effect.
Allogeneic stem-cell transplantation is currently the only method of treatment for patients with myeloproliferative neoplasm–associated myelofibrosis that has been shown to induce long-term disease-free remission.
1
Unfortunately, allogeneic stem-cell transplantation is associated with a relatively high rate of treatment-related death and complications, including chronic graft-versus-host disease. Furthermore, many older patients are not eligible for this intervention. Other treatment strategies, including the use of Janus kinase (JAK) inhibitors, are palliative and lack selective anticlonal activity.
2
Ruxolitinib and other JAK inhibitors can alleviate constitutional symptoms and reduce spleen size, but they often cannot induce complete or partial remissions, reversal of bone marrow fibrosis, . . .