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Pelabresib Plus Ruxolitinib Improves Underlying Myelofibrosis

Medically reviewed by Carmen Pope, BPharm. Last updated on March 27, 2025.

By Elana Gotkine HealthDay Reporter

THURSDAY, March 27, 2025 -- Pelabresib, a bromodomain and extraterminal domain inhibitor, plus ruxolitinib (a Janus kinase [JAK] inhibitor) improves signs of underlying myelofibrosis in JAK inhibitor-naive patients, according to a study published online March 10 in Nature Medicine.

Raajit K. Rampal, M.D., Ph.D., from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues conducted a phase 3 study (MANIFEST-2) involving JAK inhibitor-naive patients with myelofibrosis who were randomly assigned to receive pelabresib 125 mg once daily for 14 days followed by a seven-day break or to placebo combined with ruxolitinib 10 or 15 mg twice daily (214 and 216 patients, respectively).

The researchers found that the primary end point of reduction in spleen volume of ≥35 percent from baseline at week 24 was met in 65.9 and 35.2 percent of patients randomly assigned to pelabresib-ruxolitinib and placebo-ruxolitinib, respectively. The absolute change in total symptom score (TSS) was –15.99 and –14.05, respectively; a ≥50 percent decrease from baseline in TSS response at week 24 was achieved in 52.3 and 46.3 percent, respectively, for pelabresib-ruxolitinib and placebo-ruxolitinib. The most common treatment-emergent adverse events were thrombocytopenia (occurring in 52.8 and 37.4 percent, respectively) and anemia (44.8 and 55.1 percent, respectively).

"The phase 3 MANIFEST-2 study provides important insights into disease biology and modification, supporting the combination of pelabresib plus ruxolitinib for JAK inhibitor-naive patients with myelofibrosis," the authors write.

Several authors disclosed ties to pharmaceutical companies, including Novartis; the MANIFEST-2 study was funded by Constellation Pharmaceuticals, a Novartis Company.

Abstract/Full Text

Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions.

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Posted March 2025

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