MANIFEST-2 trial update: Significant improvement in SVR35 and TSS50

On November 21, 2023, topline results were released from the phase III MANIFEST-2 trial (NCT04603495) investigating pelabresib, a bromodomain and extra-terminal domain inhibitor, in combination with ruxolitinib vs placebo for Janus kinase inhibitor-naïve patients with myelofibrosis.

The study met its primary endpoint of spleen volume reduction ≥35% (SVR35) at Week 24 for patients treated with combination therapy. Significant improvements in secondary endpoints were also observed, including change in Total Symptom Score (TSS) and ≥50% reduction in TSS at Week 24 in both intermediate-risk patients (90% of cohort) and the overall patient cohort.

To learn more about current combination therapies for Janus kinase inhibitor-naïve patients with myelofibrosis, read our recent MPN Hub article.

Results¹

• Treatment with combination therapy showed a statistically significant improvement in SVR35 at Week 24
• In patients on combination therapy compared with patients on a placebo, SVR35 was achieved in 66% and 35%, respectively (p < 0.001).
• Combination therapy showed a favorable absolute change in TSS compared with placebo for both patients with intermediate-risk disease and the overall patient cohort (Figure 1).

Figure 1. Absolute TSS change in patients with intermediate-risk disease and the overall patient cohort* 

TSS, Total Symptom Score.
*Adapted from MorphoSys.¹

 Combination therapy was also favorable in ≥50% reduction in TSS for both intermediate-risk patients and the overall patient cohort compared with placebo (Figure 2).

Figure 2. TSS50 in patients with intermediate-risk disease and the overall patient cohort*

TSS50, ≥50% reduction in Total Symptom Score.
*Adapted from MorphoSys.¹

• The safety profile was consistent with previous reports, and no new safety signals were observed
  • Anemia-related adverse events were reported less frequently in patients treated with combination therapy vs placebo
• More detailed results are due to be presented at the upcoming 65th American Society of Hematology (ASH) Annual Meeting and Exposition