Myelofibrosis: Promising Combination of Pelabresib & Ruxolitinib

A new hope is looming for Myelofibrosis patients who experienced a suboptimal response to ruxolitinib and those who were JAK inhibitor naïve after presenting preliminary data from the phase 1/2 MANIFEST trial (NCT02158858). According to data that was shared during the European Hematology Association congress, the combination of pelabresib and ruxolitinib demonstrated a durable response beyond week 24. Additionally, 68% (95% CI, 57%-78%) of patients with JAK inhibitor–naïve myelofibrosis (n = 84; arm 3) experienced a reduction in spleen volume of at least 35% (SVR35) at week 24 with the combination, and 80% of patients achieved this at any point in the study. Moreover, 69% of those with SVR35 maintained response at the time of data cutoff. Interestingly, 56% (95% CI, 45%-67%) of patients in this arm experienced a 50% or greater reduction in total symptom score (TSS) from baseline at week 24, resulting in a median TSS change of –59% at this time point.

For those patients that previously experienced a suboptimal response to ruxolitinib (n = 81; arm 2), 20% experienced SVR35 at week 24; this was observed in 17% of those who were transfusion dependent (TD) and 26% of those who were non–transfusion dependent (NTD).

On a safety level, the combination of pelabresib and ruxolitinib was generally well tolerated, and preliminary results showed durable improvements in splenomegaly and symptom burden, with associated biomarker results.