Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2023
MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Myelofibrosis.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02158858 (A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins), which is not on this map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (Dose Escalation of CPI-0610 in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myeloproliferative Neoplasms)
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.Annals of medicine · 2026Pooled it
- ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis.Blood advances · 2025Trial
- Pelabresib plus ruxolitinib for JAK inhibitor-naive myelofibrosis: a randomized phase 3 trial.Nature medicine · 2025Trial
- Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.European journal of haematology · 2026Review
- Indications for Autologous and Allogeneic Hematopoietic Stem-Cell Transplantation in Adults: State of the Art.Journal of clinical medicine · 2026Review
- Thrombopoietin Receptor MPL in Hematopoiesis and Myeloproliferative Neoplasms: Physiological Roles and Pathogenic Mechanisms.Stem cell reviews and reports · 2026Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Chemical Epigenetics: Small Molecules Targeting Chromatin Modifiers in Disease Modulation.Cell biochemistry and biophysics · 2026Review
- Chemical Epigenetics: Small Molecules Targeting Chromatin Modifiers in Disease Modulation.Cell biochemistry and biophysics · 2026Review
- Phase 1b study of ABBV-744, a novel, selective BET inhibitor, as monotherapy for patients with myelofibrosis.Blood advances · 2026Article
- Review
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- The Future of Epigenetics: Emerging Technologies and Clinical Applications.ACS pharmacology & translational science · 2026Review
- A European survey on allogeneic haematopoietic cell transplantation for myelofibrosis on behalf of the Chronic Malignancies Working Party of the EBMT: focus on 'real world' experience of JAK inhibitors, splenomegaly management and novel agents in the transplant algorithm.Bone marrow transplantation · 2026Article
- Moving forward from spleen response as an endpoint in randomized controlled trials in myelofibrosis.Haematologica · 2026Review
- Epigenetic Targeting in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- Roginolisib in Combination with JAK Inhibitors in Patients with Myelofibrosis Who are Unresponsive to Approved JAK Inhibitors (Study HEMA-MED) - A Trial in Progress.OncoTargets and therapy · 2026Article
- Discovery of Anticancer Indole-Based 4,5-Dihydroisoxazole Derivative with Selectivity toward Leukemia Cells.ACS pharmacology & translational science · 2025Article
- Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives.American journal of hematology · 2025Review
- Emerging Therapeutic Approaches for Anemia in Myelofibrosis.Current hematologic malignancy reports · 2025Review
Corrections and comments
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Authors and funding
24 authors at 18 institutions in 7 countries.
Funding
Abstract
purposeStandard therapy for myelofibrosis comprises Janus kinase inhibitors (JAKis), yet spleen response rates of 30%-40%, high discontinuation rates, and a lack of disease modification highlight an unmet need. Pelabresib (CPI-0610) is an investigational, selective oral bromodomain and extraterminal domain inhibitor (BETi).
methodsMANIFEST (ClinicalTrails.gov identifier: NCT02158858), a global, open-label, nonrandomized, multicohort, phase II study, includes a cohort of JAKi-naïve patients with myelofibrosis treated with pelabresib and ruxolitinib. The primary end point is a spleen volume reduction of ≥ 35% (SVR35) at 24 weeks.
resultsEighty-four patients received ≥ 1 dose of pelabresib and ruxolitinib. The median age was 68 (range, 37-85) years; 24% of patients were intermediate-1 risk, 61% were intermediate-2 risk, and 16% were high risk as per the Dynamic International Prognostic Scoring System; 66% (55 of 84) of patients had a hemoglobin level of < 10 g/dL at baseline. At 24 weeks, 68% (57 of 84) achieved SVR35, and 56% (46 of 82) achieved a total symptom score reduction of ≥ 50% (TSS50). Additional benefits at week 24 included 36% (29 of 84) of patients with improved hemoglobin levels (mean, 1.3 g/dL; median, 0.8 g/dL), 28% (16 of 57) with ≥ 1 grade improvement in fibrosis, and 29.5% (13 of 44) with > 25% reduction in
conclusionThe rational combination of the BETi pelabresib and ruxolitinib in JAKi-naïve patients with myelofibrosis was well tolerated and showed durable improvements in spleen and symptom burden, with associated biomarker findings of potential disease-modifying activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.