Is pelabresib plus ruxolitinib the paradigm-shifting combo therapy for myelofibrosis?

Treatment with pelabresib plus ruxolitinib improved all 4 hallmarks of myelofibrosis, 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 myelofibrosis. The 430 participants with myelofibrosis were randomised to pelabresib or placebo plus ruxolitinib. The primary endpoint was a 35% spleen volume reduction (SVR35) at week 24. Dr Raajit Rampal (Memorial Sloan Kettering Cancer Center, NY, USA) presented the latest trial results [1].

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 addressed 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). Haemoglobin responses were seen in 10.7% and 6.0% of the participants in the experimental and placebo arm, respectively. 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 adverse events in the experimental and placebo arms were anaemia (43.9% vs 55.6%), thrombocytopaenia (32.1% vs 23.4%), decreased platelet count (20.8% vs 15.9%), and diarrhoea (23.1% vs 18.7%).

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

1. Rampal RK, et al. Safety and efficacy of pelabresib in combination with ruxolitinib for JAK inhibitor treatment-naïve patients with myelofibrosis: latest data from the phase 3 MANIFEST-2 study. S221, EHA congress 2024, 13–16 June, Madrid, Spain.

Copyright ©2024 Medicom Medical Publishers



Posted on 12 August 2024