Dr Mascarenhas on Ongoing Research in Myelofibrosis

John Mascarenhas, MD, professor of medicine, the Icahn School of Medicine, Mount Sinai, director, the Center of Excellence for Blood Cancers and Myeloid Disorders, member, the Tisch Cancer Institute, Mount Sinai, discusses ongoing trials and research in myelofibrosis.

Among the clinical trials currently investigating novel approaches for patients with myelofibrosis, data are emerging from studies evaluating non–JAK inhibitor approaches. For example, selinexor (Xpovio), which is approved for the treatment of select patients with multiple myeloma and other B-cell malignancies, was investigated in combination with ruxolitinib (Jakafi) in patients with myelofibrosis in a phase 1 trial (NCT04562389).

Data presented at the 2022 ASH Annual Meeting showed that patients treated with the combination experienced significantly reduced spleen volume, an improved total symptom score (TSS), and hemoglobin stabilization. Data also demonstrated that the doublet produced a manageable toxicity profile. Although more data are needed, the exploration of selinexor in the treatment of patients with myelofibrosis will be interesting to follow, Mascarenhas says.

Additionally, data have been presented on the use of navtemadlin (KRT-232), an MDM2 inhibitor, as a single-agent, and it is also being explored in combination with ruxolitinib and in combination with the BTK inhibitor TL-895. The phase 3 BOREAS trial (NCT03662126) is evaluating single-agent navtemadlin vs best available therapy in the second-line setting for patients with myelofibrosis who are relapsed/refractory to a JAK inhibitor.

Moreover, several agents are currently under exploration in combination with ruxolitinib as up-front or salvage therapy, such as parsaclisib, navitoclax (ABT-263), and pelabresib (CPI-0610), Mascarenhas says.

Accrual is ongoing for the phase 3 IMpactMF trial (NCT04576156), which is evaluating imetelstat vs best available therapy for patients with myelofibrosis who did not respond to a JAK inhibitor, Mascarenhas concludes.