Dr Mascarenhas on Key Considerations for Clinical Trial Enrollment in Myelofibrosis

"The goal of therapy obviously dictates what treatment makes sense for each individual patient. It has to be personalized."

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 important factors and potential challenges to consider when evaluating patients for clinical trial enrollment in myelofibrosis.

Mascarenhas began by emphasizing the importance of timely referral and individualized assessment when considering clinical trial enrollment for patients with myelofibrosis, particularly those with suboptimal response to JAK inhibitors such as ruxolitinib.

One of the key challenges in trial enrollment is that patients are often referred too late, when their disease has progressed and performance status has declined, making them ineligible, he noted. Early referral to participating centers for ongoing studies such as the phase 3 IMpact-MF trial (NCT04576156) is therefore critical, particularly for patients with survival prolongation as a treatment goal.

Therapeutic decisions must be personalized, taking into account not only disease biology but also the patient’s age, comorbidities, and goals of care, Mascarenhas continued. For some older or frail patients, comfort and symptom management may take precedence over aggressive intervention or clinical trial participation.

Mascarenhas also highlighted key considerations for the use of imetelstat (Rytelo), an intravenous telomerase inhibitor approved for use in lower-risk myelodysplastic syndromes and under investigation in myelofibrosis. Imetelstat is administered every 3 weeks and is associated with reversible myelosuppression, he detailed. Patients with significant baseline cytopenias may not be ideal candidates, he noted. However, for appropriate individuals, imetelstat offers a potential option beyond JAK inhibition, particularly for those seeking disease modification, improved progression-free survival, and overall survival, Mascarenhas explained. In select patients, it may also serve as a bridge to allogeneic stem cell transplantation, the only potentially curative therapy, though many patients are not eligible due to age or comorbidities, he concluded.