ASCO 2024: Pelabresib plus ruxolitinib reduces splenomegaly, improves anemia in patients with myelofibrosis

Updated data from the phase 3 MANIFEST-2 study found that pelabresib (PELA), an investigational BET inhibitor that aims to decrease expression of genes involved in myelofibrosis (MF), significantly reduced splenomegaly, showed a trend toward a reduction in tumor symptom score from baseline, and improved bone marrow fibrosis and anemia at week 24 compared with ruxolitinib (RUX) alone in JAK inhibitor-naïve patients with MF.

• As of August 31, 2023, 430 patients were randomized 1:1 and PELA or placebo was administered (QD for 14 consecutive days of 21) with RUX (bid for 21 days [1 cycle]). Primary endpoint was ≥35% spleen volume reduction from baseline (SVR35) at week 24. Secondary endpoints included absolute change in total symptom score (TSS), ≥50% reduction in TSS from baseline (TSS50), hemoglobin (Hb) response, RBC transfusion number, and bone marrow fibrosis (BMF).
• At week 24, the trial met its primary endpoint when 65.9% vs. 35.2% of patients had an SVR35 response in the PELA+RUX vs placebo+RUX arms, respectively. SVR35 responders at any time were 80.4% vs. 50.0%; 80% vs. 63% of responders reached SVR35 at week 12 scan; 83.7% vs. 79.6% maintained response at cutoff.
• In terms of secondary endpoints, mean change in absolute TSS was -15.99 vs. -14.05, and TSS50 was 52.3% vs. 46.3% at week 24. There was a 2-fold difference in patients with both SVR35 and TSS50 with PELA+RUX (40.2%) vs. placebo+RUX (18.5%). Hb response occurred in 10.7% vs 6.0% of patients, with differences in mean Hb levels maintained at 48 wks. In pts with anemia, Hb response occurred in 16.4% vs. 14.1%. A total of 30.8% vs. 39.8% of required RBC transfusion during the first 24 wks. BMF improvement ≥1 grade occurred in 38.5% vs. 24.2% of pts.
• Among 426 patients evaluated for safety, the most common treatment-emergent adverse events (≥20%) in the PELA+RUX vs. placebo+RUX arms were anemia (43.9% vs. 55.6% [Grade ≥3, 23.1% vs. 36.4%]), thrombocytopenia (32.1% vs. 23.4% [9% vs. 5.6%]), platelet count decreased (20.8% vs. 15.9% [4.2% vs. 0.9%]), and diarrhea (23.1% vs. 18.7% [0.5% vs. 1.4%]).

Source:

Rampal, R., et al. Updated safety and efficacy data from the phase 3 MANIFEST-2 study of pelabresib in combination with ruxolitinib for JAK inhibitor treatment-naïve patients with myelofibrosis. Abstract #6502. Presented at: 2024 ASCO Annual Meeting; May 31 – June 4. Chicago, IL. https://meetings.asco.org/abstracts-presentations/231688