Dr. Mascarenhas on Advancements in the Treatment Landscape of Myelofibrosis

John O. Mascarenhas, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, director, the Center of Excellence for Blood Cancers and Myeloid Disorders, member, the Tisch Cancer Institute, discusses current advancement in the treatment landscape of myelofibrosis.

Currently under development are regimens that exploit the synergy between various mechanistic pathways involved in myelofibrosis, Mascarenhas states. For example, the phase 3 MANIFEST-2 trial (NCT04603495) investigates ruxolitinib (Jakafi) plus pelabresib (CPI-0610) vs ruxolitinib and placebo in patients who are JAK inhibitor–naïve, Mascarenhas explains. The inception of the phase 3 MANIFEST-2 trial was inspired by the phase 2 MANIFEST trial (NCT02158858), Mascarenhas adds.

The BCL-2 inhibitor, navitoclax (ABT-263), and the PI3K inhibitor, parsaclisib, are also being investigated in the second line, Mascarenhas continues. Additionally, non-JAK inhibitor-based monotherapies can be used in the second line for patients who failed on ruxolitinib, Mascarenhas adds.

Overall, the treatment paradigm is expanding with JAK inhibitor-based combination strategies in earlier treatment lines, Mascarenhas concludes.