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dc.contributor.authorPalandri, F.
dc.contributor.authorMascarenhas, J.
dc.contributor.authorHarrison, C.
dc.contributor.authorPatriarca, A.
dc.contributor.authorDevos, T.
dc.contributor.authorRampal, R.
dc.contributor.authorVannucchi, A.
dc.contributor.authorPassamonti, F.
dc.contributor.authorMead, A.
dc.contributor.authorKremyanskaya, M.
dc.contributor.authorSomervaille, Tim C P
dc.contributor.authorWondergem, M.
dc.contributor.authorHoffman, R.
dc.contributor.authorLuptakova, K.
dc.contributor.authorWang, J.
dc.contributor.authorColak, G.
dc.contributor.authorShao, J.
dc.contributor.authorBobba, S.
dc.contributor.authorTrojer, P.
dc.contributor.authorVerstovsek, S.
dc.contributor.authorGupta, V
dc.date.accessioned2022-01-11T11:59:35Z
dc.date.available2022-01-11T11:59:35Z
dc.date.issued2021en
dc.identifier.citationPalandri F, Mascarenhas J, Harrison C, Patriarca A, Devos T, Rampal R, et al. CPI-0610, A BROMODOMAIN AND EXTRATERMINAL DOMAIN (BET) PROTEIN INHIBITOR, IN COMBINATION WITH RUXOLITINIB, IN JAK INHIBITOR-NAIVE MYELOFIBROSIS PATIENTS: UPDATE OF MANIFEST PHASE 2 STUDY. Haematologica. 2021;106(10):5-6.en
dc.identifier.urihttp://hdl.handle.net/10541/624818
dc.description.abstractCPI-0610 is first-in-class, oral, small-molecule inhibitor of BET proteins with potential for disease-modifying activity through altered gene regulation of key oncogenic, fibrotic, and inflammatory factors and may transform the standard of care in myelofibrosis (MF). CPI-0610 in combination with ruxolitinib (CPI-0610 +rux) is currently being studied in JAK-inhibitor (JAKi) treatment-naïve MF patients (pts) in Arm 3 of MANIFEST, a global, open-label, phase 2 study. Here we report the safety and efficacy data from Arm 3 of the ongoing MANIFEST study. Eligibility: JAKi-treatment-naïve MF pts with DIPSS score ≥Int-2; platelet ≥100 x 109 /L; spleen volume ≥ 450 cc by CT/MRI; ≥2 symptoms measurable (score ≥3) or a total symptom score (TSS) of ≥10 using the MFSAF v4.0. Primary endpoint: SVR35 response (≥35% reduction in spleen volume) at wk 24; key secondary endpoint: TSS50 response (≥50% reduction in TSS) at wk 24. As of 29 September 2020, 78 pts treated, 66 pts ongoing. Baseline characteristics: mean age: 67 years old; 72% male; primary MF: 54% pts; DIPSS ≥Int-2: 76% pts; IPSS ≥Int-2: 83%; 65% pts anemic (Hgb <10g/dL); median platelet: 294 x 109 /L (range: 100, 1849); median spleen volume: 1719 cc (range: 451, 4782); median TSS: 16 (range: 0, 38); high-molecular-risk mutations: 55% pts JAK2 mutation: 72%; ASXL1 mutation: 45%. At week 24, 67% (42/63) pts achieved SVR35 (median % change from baseline: -50%; range: - 84.4%, 23.7%) and 57% (34/60) pts achieved TSS50 (median % change from baseline: -59%; range: -100%, 225%). Additionally, 33% (16/48) of pts had at least one grade improvement in bone marrow fibrosis. 78 pts were evaluable for safety. The most common hematological TEAEs of any grade were anemia (33%, ≥Gr3: 30%) and thrombocytopenia (32%, ≥Gr3: 8%). These cytopenias were generally manageable with dose modifications. CPI-0610 + rux combination is generally well-tolerated in JAKi-treatment-naïve MF pts. The encouraging clinical data demonstrate the potential for the combination treatment to provide enhanced efficacy as evidenced by higher SVR35 and TSS50 rates at wk 24 compared with historical data from pivotal phase 3 studies. Overall, the data suggest that the addition of CPI-0610 to rux is potentially synergistic in JAKi-naïve MF pts. A phase 3, randomized, double blind, active-control study to further evaluate this combination is initiated.en
dc.language.isoenen
dc.titleCPI-0610, A bromodomain and extraterminal domain (bet) protein inhibitor, in combination with ruxolitinib, in jak inhibitor-naive myelofibrosis patients: update of manifest phase 2 studyen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentIRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologiaen
dc.identifier.journalHaematologicaen
dc.description.noteen]


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