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Pelabresib (CPI-0610) Monotherapy in Patients with Myelofibrosis - Update

Update of Clinical and Translational Data from the Ongoing Manifest Trial

November 2021

The article discusses the results of the MANIFEST Phase 2 study (NCT02158858), which investigated the use of pelabresib (CPI-0610) as a monotherapy for patients with advanced myelofibrosis (MF) who were intolerant, refractory to, or ineligible for ruxolitinib (RUX), a standard treatment for MF. Pelabresib is a selective inhibitor of bromodomain and extraterminal domain (BET) proteins, which can modify gene expression involved in nuclear factor kappa B (NFκB) signaling.


The study enrolled patients with MF who had a poor prognosis and were intolerant/refractory to or ineligible for JAK inhibitors (JAKi). The primary endpoint for transfusion-dependent (TD) patients was transfusion independence (TI) for at least 12 weeks, while the primary endpoint for non-TD patients was a spleen volume reduction (SVR) of at least 35% at week 24. Secondary endpoints included symptom reduction and safety.


Preliminary results showed that pelabresib demonstrated clinical activity in a subset of patients who were ineligible for RUX, a population with limited treatment options. The clinical benefits observed included SVR and symptom reduction. Pelabresib also showed improvements in bone marrow fibrosis and increases in hemoglobin levels.


The study also evaluated changes in plasma levels of proinflammatory cytokines, which are linked to inflammation and elevated in MF patients. Pelabresib significantly reduced the plasma levels of several cytokines in both RUX-naïve and RUX-experienced patients.

In terms of safety, the most common hematological treatment-emergent adverse events were thrombocytopenia and anemia, while the most common non-hematological adverse events included nausea, diarrhea, dysgeusia, asthenic conditions, respiratory tract infections, cough, constipation, and weight decrease.


These preliminary findings suggest that pelabresib monotherapy is generally well-tolerated and shows promising clinical activity in patients with MF who are intolerant/refractory to or ineligible for JAK inhibitors, a population with limited treatment options and poor outcomes. Further data from the study, including long-term results, will be presented in the future.


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