Author(s): Kristi Rosa
May 31, 2024
The addition of pelabresib (CPI-0610) and ruxolitinib (Jakafi) led to a significant and durable reduction in splenomegaly, showed a trend toward reduced tumor symptom score (TSS) from baseline, and improved anemia and bone marrow fibrosis at week 24 vs ruxolitinib alone in JAK inhibitor–naive patients with myelofibrosis, according to updated data from the phase 3 MANIFEST-2 study (NCT04603495) presented at the 2024 ASCO Annual Meeting.1
As previously presented at the 2023 ASH Annual Meeting, the trial met its primary end point when a higher percentage of those who received the doublet (n = 214) experienced a 35% or greater reduction in spleen volume (SVR35) at week 24 vs those given ruxolitinib alone (n = 216), at 65.9% and 35.2%, respectively (difference, 30.4; 95% CI, 21.6-39.3; P < .001).2 The mean percentage change in spleen volume at week 24 in the pelabresib/ruxolitinib arm was -50.6% (95% CI, -53.2% to -48.0%) vs -30.6% (95% CI, -33.7% to -27.5%) in the ruxolitinib-alone arm.
When looking at all responders who achieved SVR35 response, the proportion who lost response at any point in the pelabresib/ruxolitinib arm was 13.4% and more than double in the ruxolitinib-alone arm, at 27.8%. When examining the criteria of loss of SVR35 response plus a spleen volume increase greater than 25% from nadir, this occurred in 9.3% and 14.8% of patients, respectively. Notably, SVR35 response was consistently higher with the doublet vs the monotherapy across all predefined subgroups and across hematologic subgroups.
A strong trend for numerical decrease in absolute change in TSS from baseline at week 24 was observed with the doublet vs the monotherapy, at -15.99 and -14.05, translating to a mean difference of -1.94 points (95% CI, -3.92 to 0.04; P = .0545). A higher proportion of patients who received the combination vs ruxolitinib alone achieved a 50% reduction in TSS (TSS50), at 52.3% vs 46.3% (difference, 6.0; 95% CI, -3.5 to 15.5; P = .216); this difference did not reach statistical significance. A two-fold increase in patients who achieved both SVR35 and TSS50 responses was observed with pelabresib plus ruxolitinib vs ruxolitinib alone, at 40.2% and 18.5%, respectively.