Imetelstat confers durable transfusion independence in lower-risk myelodysplastic syndrome
Click Here to Manage Email Alerts
Treatment with imetelstat led to durable transfusion independence for certain heavily transfused patients with lower-risk myelodysplastic syndrome, according to study results published in Journal of Clinical Oncology.
“Telomerase is known to be active in many patients with myelodysplastic syndromes, which is associated with a poorer prognosis and may contribute to disease manifestations, including anemia,” David P. Steensma, MD, FACP, associate professor of medicine at Harvard Medical School, told Healio. “Imetelstat [GRN163L, Geron Corp.] is a first-in-class telomerase inhibitor, and phase 1 trials suggested that some patients with myeloid neoplasms had improvement in anemia.”
Limited treatment options exist for patients with lower-risk myelodysplastic syndrome who are red blood cell transfusion-dependent and relapsed after or are refractory to erythropoiesis-stimulating agents.
For the phase 2, multicenter, open-label, single-arm study, Steensma and colleagues sought to assess the safety and efficacy of imetelstat among 57 patients (median age, 71 years; range, 46-83; 56% men) with low-risk myelodysplastic syndrome. Patients received a 2-hour IV infusion of 7.5 mg/kg imetelstat every 4 weeks until disease progression, unacceptable toxicity, withdrawal of consent or failure to respond.
Median treatment duration was 8.2 months, with a median eight treatment cycles.
Eight-week red blood cell transfusion independence rate served as the primary endpoint. Secondary endpoints included 24-week red blood cell transfusion independence rate, transfusion independence duration, hematologic improvement-erythroid response rate and safety.
Median follow-up was 16.4 months for the overall population and 15.7 months among a subset of 38 patients who were non-del(5q) and had not been treated with a hypomethylating agent or lenalidomide (Revlimid, Bristol Myers Squibb).
By the time of data cutoff, 43 patients had discontinued treatment due to lack of treatment efficacy (28%), adverse events (25%), withdrawal by patient or patient refusal (11%), progressive disease (5%), death (4%), relapse as a result of recurrent transfusion dependence and physician decision (2%).
Study results showed red blood cell transfusion independence rates of 37% (n = 21) at 8 weeks and 23% (n = 13) at 24 weeks among the overall population, with a median transfusion independence duration of 65 weeks. Red blood cell transfusion independence rates among the subset of non-del(5q) and hypomethylating agent/lenalidomide-naive participants were 42% (n = 16) at 8 weeks and 29% (n = 11) at 24 weeks, with a median transfusion independence duration of 86 weeks.
In addition, cytogenic and mutational data indicated a decrease in malignant clones, which suggested disease modification activity, according to the researchers.
Safety appeared comparable between the overall and subset populations, with 94% of patients in the subset population experiencing at least one treatment-emergent adverse event and 82% experiencing at least one grade 3 or higher treatment-emergent adverse event. The most common adverse events included neutropenia and thrombocytopenia, which stopped when treatment ceased.
“Imetelstat is associated with freedom from transfusion for at least 2 months in almost 40% of patients with lower-risk myelodysplastic syndrome who require transfusions regularly and who have not yet had lenalidomide or a hypomethylating agent. In addition, the mutation burden, or disease clone, declines in some responding patients,” Steensma said. “An ongoing phase 3 trial of imetelstat vs. supportive care alone in patients with transfusion-requiring, myelodysplastic syndrome-associated anemia is currently enrolling patients. If the study is positive, it will hopefully lead to regulatory approval for a myelodysplastic syndrome indication and a new option for this population of patients.”
For more information:
David P. Steensma, MD, FACP, can be reached at Harvard Medical School, 450 Brookline Ave., Boston, MA 02215; email: david_steensma@dfci.harvard.edu.
Collapse
Read more about
Click Here to Manage Email Alerts