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Long-term follow-up data from the phase 3 MANIFEST 2 clinical trial have been revealed.
Among Janus kinase (JAK) inhibitor-naïve patients with myelofibrosis, treatment with the combination of pelabresib and Rituxan (ruxolitinib), when compared with patients who received placebo and Rituxan, resulted in clinically meaningful benefits, researchers have reported.
Seventy-two-week follow-up data with long-term efficacy outcomes for the phase 3 MANIFEST-2 clinical trial were presented by Dr. Alessandro Maria Vannucchi of the University of Florence in Florence, Italy, during the European Hematology Association 2025 Congress held in Milan.
Notably, more of the patients treated with pelabresib and Rituxan (214 patients) experienced improvements in spleen volume compared to those (216 patients) in the trial’s placebo arm, with respective rates of spleen volume reduction of 35% or greater at week 72 being 43.3% and 29.2%. Similarly, the mean changes in spleen volume between the two arms at week 72 were 57.2% and 34.9%, Vannucchi reported at the meeting.
Anemia: a low count of healthy red blood cells.
Thrombocytopenia: a low count of platelets.
Overall survival: the time a patient lives, regardless of disease status.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Furthermore, it was found that more patients in the pelabresib arm maintained their spleen volume reduction responses, with 22.7% of that arm losing their response versus 25.8% of responders in the placebo arm. Vannucchi reported that 80% of patients in the pelabresib arm and 73% of patients in the placebo arm maintained their response for 72 weeks.
Myelofibrosis, as explained by the MPN Research Foundation, is a chronic blood cancer classified as a myeloproliferative neoplasm, or MPN, which involves the formation of excessive scar tissue in the bone marrow, impairing the body’s ability to produce normal blood cells. Subsequently, blood cell production may move to the spleen, in turn causing spleen enlargement.
Both spleen volume reduction of at least 35% and an at least 50% reduction in total symptom score were experienced by 31.3% of patients in the pelabresib arm, versus 17.6% of patients in the placebo arm, it was reported.
Vannucchi showed that 16.4% of patients in the pelabresib arm, versus 9.3% of patients in the placebo arm, displayed hemoglobin responses, and noted that fewer patients in the former arm required red blood cell transfusions over the course of 72 weeks. Additionally, a bone marrow fibrosis improvement was shown in 51.4% of patients in the pelabresib arm and 28.2% of patients in the placebo arm at week 72.
Regarding side effects, the most frequent treatment-related side effects in both arms of the study were less than grade 3 (severe). In the pelabresib arm, anemia and thrombocytopenia of any grade were experienced by 51.4% and 57.5% of patients, respectively. Those rates were 58.4% and 44.9% in the placebo arm, respectively.
Concerning overall survival, at 72 weeks there were 23 deaths in the pelabresib arm and 27 deaths in the placebo arm. At the 72- week data cutoff, there were 21 and 27 progression-free survival events in the two arms, respectively.
As reported by CURE earlier this year, pelabresib treatment in combination with Rituxan was found to be safe, well tolerated, and improved signs of underlying myelofibrosis pathobiology, as well as provided substantial clinical benefit over standard-of-care therapy with a JAK inhibitor among patients with myelofibrosis, according to findings from the MANIFEST-2 trial which were published in the journal Nature Medicine.
“This is one of the largest myelofibrosis clinical trials to date,” lead study author, Dr. Raajit Rampal, stated in a news release from Memorial Sloan Kettering Cancer Center in New York. “There is a real unmet need for patients with this disease, and the findings from this trial represent an exciting advance.”
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