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John O. Mascarenhas, MD, discussed findings from the IMproveMF trial investigating imetelstat plus ruxolitinib in patients with higher-risk myelofibrosis.
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“We have some preliminary efficacy data demonstrating spleen responses, symptom responses, and even reductions in driver mutations, including JAK2, CALR, and subclonal, high-risk mutations like ASXL1. We’ve seen this in the [imetelstat] monotherapy [and] relapsed/refractory settings, but [these are] really the first data demonstrating the tolerability, earlier on, with ruxolitinib and the ability to get these kinds of clinical outcome measures, [such as] spleen [response], symptom [improvement], and [measurement of] biomarkers of disease modification like reduction of JAK2.”
John O. Mascarenhas, MD, a professor of medicine at the Icahn School of Medicine at Mount Sinai; as well as director of the Center of Excellence for Blood Cancers and Myeloid Disorders, director of the Adult Leukemia Program, and a member of The Tisch Cancer Institute, discussed efficacy findings and next steps for the phase 1/1b IMproveMF trial (NCT05371964) investigating imetelstat (Rytelo) plus ruxolitinib (Jakafi) in patients with intermediate-1, intermediate-2, and high-risk myelofibrosis.
Preliminary efficacy data demonstrated clinical responses like spleen volume response (SVR), symptom improvement, and decreases in driver mutations—including JAK2, CALR, and high-risk subclonal mutations like ASXL1, according to Mascarenhas. Across all 4 imetelstat dose cohorts included in the study, investigators observed trends toward a reduction from baseline total symptom score over 12 weeks, as well as toward dose-dependent SVR. These findings, previously observed with imetelstat monotherapy and in the relapsed/refractory myelofibrosis setting, represent the first evidence of the tolerability and potential disease modification associated with this agent when combined with ruxolitinib in earlier treatment phases, he said.
As this cohort expands, further efficacy findings will include bone marrow fibrosis grading, marrow cellularity, mutational burden, and levels of circulating CD34-positive cells, Mascarenhas explained. The durability of treatment, patient retention on therapy, and sustained clinical benefit are key objectives of the phase 1b component, he stated. Additionally, part 2 of the study is now enrolling JAK inhibitor–naive patients to evaluate the upfront combination of imetelstat and ruxolitinib, aligning with broader efforts to assess early intervention strategies in myelofibrosis, he concluded.
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