The following is a summary of “MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Myelofibrosis,” published in the November 2023 issue of Oncology by Mascarenhas, et al.
For a MANIFEST study, researchers sought to evaluate the efficacy and safety of pelabresib (CPI-0610), an investigational bromodomain and extraterminal domain inhibitor (BETi), in combination with ruxolitinib for treating myelofibrosis in JAKi-naïve patients.
The study, a global, open-label, nonrandomized, multicohort, phase II trial, enrolled 84 patients with a median age of 68 (range, 37-85) years. The primary endpoint was achieving a spleen volume reduction of ≥ 35% (SVR35) at 24 weeks.
Results indicated that at 24 weeks, 68% of patients (57 of 84) achieved SVR35, and 56% (46 of 82) experienced a total symptom score reduction of ≥ 50% (TSS50). Additional benefits at week 24 included 36% of patients (29 of 84) showing improved hemoglobin levels (mean, 1.3 g/dL; median, 0.8 g/dL), 28% (16 of 57) with ≥ 1-grade improvement in fibrosis, and 29.5% (13 of 44) with > 25% reduction in JAK2V617F-mutant allele fraction, with a significant association to SVR35 response (P = .018). At 48 weeks, 60% (47 of 79) of patients demonstrated SVR35 response. Grade 3 or 4 toxicities included thrombocytopenia (12%) and anemia (35%), leading to treatment discontinuation in three patients. Remarkably, 95% (80 of 84) of participants continued the combination therapy beyond 24 weeks.
In conclusion, the combination of pelabresib and ruxolitinib in JAKi-naïve myelofibrosis patients demonstrated well-tolerated and durable improvements in spleen and symptom burden, with potential disease-modifying activity indicated by associated biomarker findings.