Citations 2
PAXIS: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Study (Part 1) Followed by an Open-Label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients with VEXAS Syndrome
Beck, David B. , Heiblig, Maël , Savic, S., Ferrada, Marcela A. , Mekinian, Arsène, Chowdhury, Onima , Hammond, Danielle E., Weeks, Lachelle D., Gurnari, Carmelo , Kirino, Yohei , Georgin-Lavialle, Sophie, Buckley, Sarah A., Garcha, Raman, Harder, Bryan G., Harder, Bryan , Weeks, Lachelle D. , Mékinian, A. , Savic, Sinisa , Hammond, Danielle , Georgin‐Lavialle, Sophie , Savic, Sinisa , Mékinian, Arsène , Hammond, Danielle , Weeks, Lachelle Dawn , Georgin-Lavialle, Sophie , Buckley, Sarah A , Harder, Bryan G , Koster, Matthew J , Gurnari, Carmelo , Kirino, Yohei , Heiblig, Mael , Ferrada, Marcela A , Koster, Matthew J.
Journal of Clinical Medicine | February 11, 2026 | Volume: 15 | Issue: 4 | Pages: 1426
VEXAS (Vacuoles, E1 ubiquitin-activating enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a systemic disorder characterized by an overlap of hematologic and inflammatory features. Most patients require chronic use of moderate-to-high doses of glucocorticoids (GCs) to maintain disease control. Data on GC-sparing therapies is limited, and there have been no prospective pharmacotherapeutic trials in VEXAS syndrome published to date. Pacritinib, an oral inhibitor of IRAK1, JAK2, and ACVR1, has emerged as a promising therapeutic option for VEXAS syndrome. The PAXIS trial is the first prospective, randomized pharmacotherapeutic study conducted in this rare and severe disease. Utilizing a novel study design and disease-specific endpoints, the trial will evaluate the efficacy and safety of two dose levels of pacritinib compared with placebo in patients with VEXAS syndrome (NCT06782373, EUCTR: 2024-516347-41-00).
Incorporation of Genomic Determinants Improves Diagnostic Accuracy of Oligomonocytic Chronic Myelomonocytic Leukemia
Montalban-Bravo, Guillermo, Wu, Chong , Rodríguez‐Sevilla, Juan José , Wei, Yue , Chien, K., Bouligny, Ian , Kanagal‐Shamanna, Rashmi , Li, Ziyi , Natu, Anuya , Bazinet, Alexandre , Hammond, Danielle E., Bataller, Alex, Borthakur, Gautam, Short, Nicholas J., DiNardo, Courtney D., Kadia, Tapan M., Ravandi, Farhad, Daver, Naval, Pemmaraju, Naveen, Jabbour, Elias, Issa, Ghayas C., Wang, Sa A., Patel, Keyur P. , Tang, Guilin, Medeiros, L. Jeffrey, Finke, Christy M. , Al‐Kali, Aref , Alkhateeb, Hassan, Gangat, Naseema, Mangaonkar, Abhishek A., Román, David , Arenillas, Leonor , Tefferi, Ayalew, Kantarjian, Hagop M., Garcia-Manero, Guillermo, Calvo, Xavier , Patnaik, Mrinal M. , Loghavi, Sanam, Kantarjian, Hagop M. , Bravo, Guillermo Montalban , Chien, Kelly , Gurney, Mark , Bazinet, Alexandre , Hammond, Danielle , Bataller, Alex , Borthakur, Gautam , Short, Nicholas , DiNardo, Courtney , Kadia, Tapan M , Ravandi, Farhad , Daver, Naval , Pemmaraju, Naveen , Jabbour, Elias , Issa, Ghayas , Wang, Sa A , Patel, Keyur P , Tang, Guilin , Medeiros, L Jeffrey , Lasho, Terra L , Finke, Christy M , Al-Kali, Aref , Csizmar, Clifford , Alkhateeb, Hassan B , Gangat, Naseema , Mangaonkar, Abhishek A. , Roman-Bravo, David , Arenillas, Leonor , Tefferi, Ayalew , Kantarjian, Hagop , Garcia-Manero, Guillermo , Calvo, Xavier , Patnaik, Mrinal , Loghavi, Sanam , Kanagal-Shamanna, Rashmi , Rodríguez-Sevilla, Juan José , Montalban‐Bravo, Guillermo , Chien, Kelly S. , Gurney, Mark E. , Hammond, Danielle , Borthakur, Gautam , Short, Nicholas J. , DiNardo, Courtney D. , Kadia, Tapan M. , Daver, Naval , Pemmaraju, Naveen , Jabbour, Elias , Wang, Sa A. , Tang, Guilin , Medeiros, L. Jeffrey , Lasho, Terra L. , Csizmar, Clifford M. , Alkhateeb, Hassan B. , Gangat, Naseema , Mangaonkar, Abhishek A. , Tefferi, Ayalew , Garcia‐Manero, Guillermo , Loghavi, Sanam
Blood Cancer Discovery | January 26, 2026 | Volume: 7 | Issue: 3 | Pages: 414-430
Abstract Recent updates to monocyte count thresholds recognize oligomonocytic chronic myelomonocytic leukemia (OM-CMML) as an early form of CMML. However, the clinical validity of these changes remains uncertain without incorporating biological and genomic factors. In this study, we analyzed a cohort of 911 patients (249 with OM-CMML, 359 with overt CMML, and 303 with myelodysplastic syndromes) using unsupervised clustering to evaluate the role of genomic determinants in refining CMML diagnosis. Our findings show that CMML molecular signatures (biallelic TET2 mutations or SRSF2-TET2 comutations) are linked to a distinct transcriptome, monocytic bias, classical monocytosis, and a higher risk of progression to overt CMML in OM-CMML cases. We developed a weighted genomic model and diagnostic workflow showing that combining genomic signatures with bone marrow monocyte frequencies in OM-CMML more accurately predicts progression to overt CMML. These findings support integrating genomic determinants and our clinic-ready diagnostic workflow into the CMML diagnostic framework to improve accuracy. Significance: Through comprehensive clinical and genomic profiling of a large patient cohort, alongside immunophenotypic and transcriptional cellular analyses, this study provides evidence that incorporating genomic determinants into the diagnostic criteria for OM-CMML improves diagnostic accuracy and refines the identification of early-stage CMML, thereby preventing misclassification.