Pelabresib (CPI-0610) improved anemia associated with myelofibrosis: interim results from the ongoing MANIFEST phase 2 study
Bose, P. Verstovsek, S. Kremyanskaya, M. Mascarenhas, J. Talpaz, M. Harrison, C. Rampal, R. Patriarca, A. Gupta, V. Granacher, N.
Bose, P.
Verstovsek, S.
Kremyanskaya, M.
Mascarenhas, J.
Talpaz, M.
Harrison, C.
Rampal, R.
Patriarca, A.
Gupta, V.
Granacher, N.
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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.
Description
Date
2021
Publisher
Collections
Keywords
Type
Other
Citation
Bose P, Verstovsek S, Kremyanskaya M, Mascarenhas J, Talpaz M, Harrison C, et al. Pelabresib (CPI-0610) Improved Anemia Associated with Myelofibrosis: Interim Results from the Ongoing MANIFEST Phase 2 Study. Clinical Lymphoma Myeloma & Leukemia. 2021;21:S361-S2.