Is Pelabresib + Ruxolitinib the Paradigm-Shifting Combo Therapy for Myelofibrosis?

Jul 11, 2024

Photo Credit: Md Babul Hosen

Pelabresib plus ruxolitinib has shown efficacy in the treatment responses of patients with myelofibrosis.

Treatment with pelabresib plus ruxolitinib was associated with improvements in all four hallmarks of myelofibrosis (MF), results of the phase 3 MANIFEST-2 trial showed.

The phase 3 MANIFEST-2 study (NCT04603495) evaluated pelabresib, an investigational bromodomain and extra-terminal domain (BET) protein inhibitor, in combination with JAK inhibitor ruxolitinib for treating MF. The 430 enrolled participants with MF were randomly assigned to pelabresib plus ruxolitinib or to ruxolitinib plus placebo. The primary endpoint was a 35% spleen volume reduction (SVR35) at week 24. Dr. Raajit Rampal, MPN, Memorial Sloan Kettering Cancer Center, in New York, presented the latest trial results.

At week 24, 65.9 % and 35.2 % of the participants in the pelabresib arm and placebo arm, respectively, achieved the primary endpoint (P<0.001). Dr. Rampal shared that the mean absolute change in total symptom score at week 24 was -15.99 in the pelabresib and -14.05 in the placebo arm, reflecting a numerical benefit for the pelabresib arm (P=0.055). Hemoglobin responses were seen in 10.7% and 6.0% of the participants in the experimental and placebo arm. Furthermore, significant improvements in bone marrow fibrosis (at least 1 grade) were documented for 38.5% on pelabresib and 24.2% on placebo (OR 2.09; 95% CI 1.14–3.93).

As for safety, the most common treatment-emergent AEs in the experimental and placebo arms were anemia (43.9% vs 55.6%), thrombocytopenia (32.1% vs 23.4%), decreased platelet count (20.8% vs 15.9%), and diarrhea (23.1% vs 18.7%).

In conclusion, the treatment regimen of pelabresib plus ruxolitinib was associated with significant spleen responses, improved anemia and bone marrow fibrosis, and a trend towards improved symptoms, compared to a treatment regimen of ruxolitinib and placebo in a population of patients with MF.

Medical writing support was provided by Robert van den Heuvel.