Pelabresib (CPI-0610) improved anemia associated with myelofibrosis: interim results from the ongoing MANIFEST phase 2 study

Abstract

Pelabresib (CPI-0610), a first-in-class, oral, small molecule inhibitor of BET proteins, has the potential to promote disease-modifying activity through altered gene regulation of key oncogenic, fi brotic, and infl ammatory factors in MF. Many patients (pts) with MF treated with ruxolitinib (rux) develop worsening anemia and may become RBC transfusion-dependent (TD). Objective: Evaluation of pelabresib monotherapy or as add on to rux in advanced MF pts. Design: In Arm 1, pts refractory, intolerant, or ineligible for JAKi were treated with pelabresib monotherapy. In Arm 2, pts receiving rux but not deriving adequate benefi t were treated with add-on pelabresib. The primary endpoint was achievement of transfusion independence (TI) 12 wks in TD cohorts and 35% spleen volume reduction at wk 24 in non-TD cohorts. Results: As of 29 Sept. 2020, 19 TD pts and 27 non-TD pts were treated in Arm 1. Seventy-six percent of pts had baseline Hgb <10g/dL (median: 9, range: 6–15). In the TD cohort, 21% (3/14) of pts achieved TI (median duration: 44 wk, range: 32–50). In the non-TD cohort, a mean Hgb increase 1.5 g/dL sustained over a 12-wk transfusion-free period was achieved by 59.1% (13/22) of pts. In Arm 2, 52 TD pts and 26 non-TD pts were treated with pelabresib as add-on to rux. Seventy-six percent of pts had baseline Hgb <10g/dL (median: 9, range: 6–13). In the TD cohort, 36% (13/36) pts achieved TI (median duration: 39 wk, range: 18–148); 17.4% (4/23) of non-TD pts had mean Hgb increase 1.5 g/dL sustained over a 12-wk transfusion-free period. Hgb improvement/ achievement of TI has been associated with increased reticulocyte count and/or CD71+ progenitor cells in bone marrow, suggesting a positive effect on erythroid differentiation. Pelabresib was generally well tolerated. Conclusions: Pelabresib monotherapy was associated with a mean increase in Hgb 1.5 g/dL in majority of non-TD pts and conversion of one-fifth of TD pts to TI in Arm 1. Pelabresib add-on to rux in Arm 2 resulted in mean increase in Hgb 1.5 g/dL in 17% of non-TD pts and conversion to TI in more than one-third of TD pts.