The FDA has granted a fast track designation to imetelstat for the treatment of adult patients with relapsed or refractory myelofibrosis who have intermediate-2 or high-risk disease. This designation is inclusive of patients with primary MF or those who developed MF after thrombocythemia or polycythemia vera, according to a press release from Geron Corporation, the developer of the drug.<br />
The FDA has granted a fast track designation to imetelstat for the treatment of adult patients with relapsed or refractory myelofibrosis (MF) who have intermediate-2 or high-risk disease. This designation is inclusive of patients with primary MF or those who developed MF after thrombocythemia or polycythemia vera, according to a press release from Geron Corporation, the developer of the drug.1
The drug is under investigation in this population in the ongoing phase II IMbark study, for which overall survival (OS) data were presented at the 2018 American Society of Hematology (ASH) Annual Meeting.
Imetelstat is a novel, potent telomerase inhibitor, administered by intravenous infusion. Based on preclinical data, imetelstat may have disease-modifying activity, and as a result, it is being developed in hematologic malignancies.1
The randomized multicenter, phase II IMbark trial enrolled 107 patients at 55 institutions. Two doses of imetelstat were administered to patients with MF, who are relapsed/refractory to janus kinase (JAK) inhibition. The primary endpoints for the study were spleen response rate and symptoms response rate.
The results show that the arm receiving imetelstat 4.7 mg/kg every 3 weeks had a median OS of 19.9 months. The median OS in the 9.4 mg/kg arm has not yet been reached. At 18-month follow-up, patients in the study had survival rates of 76.7% and 62.9%.2
Toxicities were considered acceptable by the investigators. In the 9.4 mg/kg arm, the adverse events (AEs) were thrombocytopenia (49%), anemia (44%), neutropenia (36%), and nausea (34%). For patients receiving 4.7 mg/kg of imetelstat, the AEs were diarrhea (38%), nausea (31%), anemia (31%), and thrombocytopenia (23%). Additionally, grade 3 and 4 AEs, such as neutropenia and thrombocytopenia, were seen more frequently in the 9.4mg/kg arm.2
These data show potential improvement in outcomes for patients with MF who are relapsed or refractory to JAK inhibition. Previous data show that OS in these patients was about 14 months.3
Based on the data from IMbark, investigators consider imetelstat to be a promising agent for patients with MF who were previously treated with JAK inhibitors. Geron announced its plans to hold an End of Phase 2 meeting with the FDA by the end of first quarter 2020.
References
Connecting Spleen Volume Reduction to Survival Outcomes in MF
April 21st 2024During a Case-Based Roundtable® event, Raajit K. Rampal, MD, PhD, discussed the correlation between spleen volume responses and survival outcomes for patients with myelofibrosis in the second article of a 2-part series.
Read More
Savona Discusses First-Line JAK Inhibition for Patients With Myelofibrosis at Risk of Anemia
April 17th 2024During a Case-Based Roundtable® event, Michael Savona, MD, and participants discussed the case of a patient with myelofibrosis and moderate anemia receiving JAK inhibitor therapy.
Read More
PTCy Offers New Hope for Mismatched Stem Cell Transplants in Leukemia, MDS
April 13th 2024Jeff Auletta, MD, discussed how PTCy-based graft-vs-host disease prophylaxis offers a promising approach for expanding access to successful cell transplantation regardless of donor match or patient ethnicity.
Read More
Scott Evaluates Treatment Options for Hydroxyurea-Resistant Polycythemia Vera
March 28th 2024In a Community Case Forum event in partnership with the Washington State Medical Oncology Society, Bart Scott, MD, broke down various trials of hydroxyurea, ruxolitinib, and interferon in patients with polycythemia vera to assess outcomes such as hematocrit control and molecular response.
Read More