MANIFEST-2: Primary analysis of pelabresib plus ruxolitinib in JAKi-naïve patients with MF

There remains an unmet need for novel treatment combinations for patients with MF due to the limited depth and durability of response and frequent TEAEs associated with JAKi monotherapy.¹

The primary analysis from the phase III MANIFEST-2 trial (NCT04603495) evaluating the efficacy and safety of BET inhibitor pelabresib + ruxolitinib vs ruxolitinib + placebo in JAKi-naïve patients with MF was published in Nature Medicine by Rampal et al.¹ Among all patients (N = 430), 214 were treated with pelabresib + ruxolitinib and 216 were treated with placebo + ruxoltitinib.¹

The primary endpoint was splenic response at Week 24 and key secondary endpoints included absolute change in TSS and TSS50 at Week 24.¹

At Week 24, the absolute change in TSS was −15.99 vs −14.05 (difference, (−1.94; 95% CI, −3.92 to 0.04; p = 0.0545) and TSS50 was achieved in 52.3% vs 46.3% (difference, 6.0%; 95% CI -3.5–15.5) of patients in the pelabresib + ruxolitinib vs ruxolitinib + placebo groups, respectively.

These findings highlight the potential of pelabresib + ruxolitinib as a first-line combination therapy for JAKi-naïve patients with MF, offering disease modification and a substantial clinical benefit vs SoC JAKi monotherapy, while maintaining a manageable safety profile.