Dr Gerds on Notable Ongoing Clinical Trials in Myelofibrosis

“There are several large studies ongoing in the myelofibrosis world that we’re eagerly awaiting additional [or initial] results from.”

Aaron T. Gerds, MD, MS, an assistant professor in the Department of Medicine at the Case Western Reserve University School of Medicine; the deputy associate director for Clinical Research and a member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center; and a physician in the Department of Hematology and Medical Oncology at Cleveland Clinic, discussed ongoing research for the treatment of patients with myelofibrosis.

One key trial awaiting additional results is the randomized phase 3 IMpactMF trial (NCT04576156) of imetelstat (Rytelo) for the treatment of patients with high-risk myelofibrosis, Gerds began. The reason for the anticipation surrounding this study is that the trial uses overall survival (OS) as the primary end point, which Gerds described as a bold and needed move in the field. Although established myelofibrosis trial end points such as spleen volume response and symptom burden response are important, they are considered imperfect, he said. Evaluating symptoms and symptom burden improvement is tricky, he noted. This challenge is compounded when the comparator arm in such studies is a JAK inhibitor such as ruxolitinib (Jakafi). The IMpactMF study, which is being conducted in the post-JAK inhibitor setting, asks the straightforward question: Can imetelstat improve OS?

Another key trial readout will be from the phase 3 INDEPENDENCE study (NCT04717414) of luspatercept-aamt (Reblozyl) in patients with myelofibrosis-associated anemia, according to Gerds. Topline results announced via a news release indicated that the trial did not meet its primary end point. Notably, luspatercept is already FDA approved for managing anemia associated with myelodysplastic syndromes. INDEPENDENCE was intended to expand luspatercept’s label to officially include myelofibrosis, Gerds continued. However, given that it missed its primary end point, a major question remains regarding the path forward for label expansion and what key secondary end points were achieved, he stated.

Several other randomized phase 3 trials are also ongoing, Gerds explained. These include the phase 3 SENTRY trial (NCT04562389) investigating selinexor (Xpovio) plus ruxolitinib in JAK inhibitor–naive patients with myelofibrosis, and the phase 3 POIESIS trial (NCT06479135) examining the MDM2 inhibitor navtemadlin as an add-on to ruxolitinib in JAK inhibitor–naive patients with myelofibrosis who have a suboptimal response to ruxolitinib. Lastly, there is continuous analysis and follow-up underway for the phase 3 MANIFEST-2 trial (NCT04603495), which is comparing ruxolitinib monotherapy vs ruxolitinib combined with the BET inhibitor pelabresib (CPI-0610), Gerds reported. Although initial and subsequent follow-up results have been presented, critical end points including event-free survival and OS may require more time to mature, he noted. This is partially because a significant number of patients in the study had intermediate-1 risk disease, he concluded.