Jakafi (ruxolitinib) / Novartis, Incyte - LARVOL DELTA

Inflammatory mediators differentially regulate megakaryopoiesis and thrombopoiesis in myelofibrosis and essential thrombocythemia. (PubMed, Sci Rep) - "MF plasma increased megakaryocyte output, which was attenuated in sequential samples from ruxolitinib-treated patients...Elevated levels of circulating RANTES correlated with ET plasma-induced proplatelet formation, which was partially reverted by RANTES receptor CCR5 antagonist Maraviroc, indicating RANTES is involved in this process. These findings indicate that, in addition to clonal mutations, extrinsic inflammatory mediators play a direct role in MF and ET megakaryocyte abnormalities. The distinct cytokine profile could potentially be useful for the development of targeted therapies."

Journal • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • BCL2L1 • CD34 • IL1B • IL6 • JAK1

Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH) (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Jerry Lee, MD, MSc, MPhil | Suspended ➔ Recruiting | Trial completion date: Nov 2027 ➔ Nov 2029

Enrollment open • Trial completion date • Hemophagocytic lymphohistiocytosis • Immunology • Rare Diseases

Comparing the diagnosis, disease, and treatment experience of essential thrombocythemia from clinicians' and patients' perspectives: Insights from a qualitative interview study in the United States (ASH 2025) - "At the time of the interviews, all patients had received hydroxyurea, with 7 currently receiving it, including 6 as first-line therapy. Two were receiving ruxolitinib, and 1 was receiving peginterferon alfa-2a... This study uncovered several gaps between specialists' and patients' perspectives across the ET disease journey. Patients described more complex and prolonged diagnostic experiences than specialists reported. While specialists generally perceived patients with ET having minimal symptoms, patients reported persistent symptoms that significantly impacted their HRQoL."

Clinical • Interview • Acute Myelogenous Leukemia • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Musculoskeletal Pain • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • Thrombosis

Understanding the essential thrombocythemia diagnosis journey, treatment experience, disease burden, and unmet need: Insights from a qualitative interview study with patients in the United States (ASH 2025) - "At the time of the interview, all 10 patients had been exposed to hydroxyurea (HU) with 6 patients receiving it as their first-line treatment. The remaining 4 were on second-line treatment, including 1 who was on HU after receiving anagrelide and others who had transitioned to alternative cytoreductive agents, including 2 on ruxolitinib and 1 on peginterferon alfa-2a following prior use of HU... Some patients reported persistent symptoms, including fatigue, which are associated with impaired HRQoL in areas of physical functioning, cognitive abilities, the ability to work, daily activities, and emotional well-being. Some patients identified prolonged diagnostic journey requiring multiple referrals and healthcare visits as well as seeking additional opinions and specialized care. Patients identified unmet needs in current treatments, namely poor symptom control, and significant side effects."

Clinical • Interview • Acute Myelogenous Leukemia • Chronic Eosinophilic Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Mood Disorders • Musculoskeletal Pain • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis

Upstream integration of implementation planning in clinical trials through the blood and marrow transplant clinical trials network (ASH 2025) - "Using the designed D+I process flow, a current effort used a survey sent to US CIBMTR centers, to evaluate factors influencing the implementation of results of the BMT CTN 1703 trial of post-transplant cyclophosphamide as graft-versus-host disease (GvHD) prophylaxis and assessed dissemination and adoption considerations for the upcoming BMT CTN 2203 CT of ruxolitinib as GvHD prophylaxis. With the existing structure of the BMT CTN and associated practice registry of the CIBMTR, the BMT CTN D+I Committee developed a systematic process to build D+I considerations into trial workflows to increase real-world impact. This process aims to ensure that barriers to uptake of trial results can be identified and addressed appropriately, improving care quality for patients undergoing TCT."

Clinical • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

Enhanced antileukemic activity of momelotinib in combination with venetoclax and azacitidine compared to gilteritinib-based combination (ASH 2025) - "Despite extensive genomic insights, conventional chemotherapies, specifically anthracyclines and cytarabine , have remained the cornerstone of treatment for the past four decades...In contrast, selective inhibitors of JAK-STAT (ruxolitinib) or FLT3 (gilteritinib or quizartinib) alone failed to demonstrate comparable synergy, highlighting the distinct polypharmacological profile of momelotinib in mediating the cytotoxic response...Notably, while the efficacy of gilteritinib-based regimens was restricted to FLT3-mutant AML, the momelotinib combination demonstrated activity across both FLT3 mutant and FLT3 wild-type contexts. Altogether these preclinical data support clinical evaluation of momelotinib in combination with venetoclax and azacitidine as a potential effective treatment in AML."

Combination therapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ACVR1 • FLT3 • IRAK1

First-line treatment with low-dose ruxolitinib, pirfenidone, and low-dose calcineurin inhibitors leads to significant improvement in patients with bronchiolitis obliterans syndrome after allogeneic transplantation (ASH 2025) - "Traditional treatments for BOS rely on glucocorticoids combined with FAM regimens ( fluticasone + azithromycin + montelukast ) and calmodulin phosphatase inhibitors ( CNIs ), but they have limited efficacy with an even lower overall remission rate ( ORR ) and poor prognosis once progression to steroid-refractory cGVHD (SR-cGVHD) is achieved...Methods A retrospective analysis of 14 patients, 11 males and 3 females, with a median age of 19 years (7-54 years), who underwent hematopoietic stem cell transplantation combined with BOS at Henan Cancer Hospital from 2018 to 2025, including 6 cases of mild BOS, 3 cases of moderate BOS, 5 cases of severe BOS, Among them, 6 cases of mild, 3 cases of moderate, and 5 cases of severe BOS were treated with low-dose rucotinib ( 5 mg qd po) combined with piroxicam (200 mg tid po), small-dose CNI (half of the effective therapeutic concentration), and FAM first-line treatment...Conclusions In conclusion, the first-line treatment of BOS..."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Transplantation

Real-world effectiveness of belumosudil for chronic GVHD by line of treatment: Analysis of academic and community practice patterns (ASH 2025) - "The most common treatment prior to BEL was ruxolitinib (RUX) alone or in combination with calcineurin inhibitors (CNIs) or glucocorticoids (GCs), which was consistent across all LOTs. These real-world data demonstrate consistent use of BEL across practice settings, including frequent use of BEL subsequent to treatment with RUX and GCs. The extent of concurrent use of BEL and RUX remains to be further elucidated before the frequency of this approach in real-world management of advanced cGVHD can be fully characterized. In spite of common use of RUX in pre-BEL LOT, ROCKreal data confirm clinically significant 6 month response rates in patients receiving BEL in LOT 3 and LOTs 4-6."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Early detection of emerging safety signals in GVHD prophylaxis agents using a 12-year faers "slope-watch" approach (ASH 2025) - "In addition to tacrolimus and cyclosporine, contemporary prophylaxis regimens employ sirolimus and everolimus, mycophenolate mofetil, methotrexate, post-transplant cyclophosphamide (PTCy), JAK inhibitors (ruxolitinib, baricitinib, tofacitinib), co-stimulation blockade with abatacept, gut-homing integrin antagonism via vedolizumab, and the ROCK2 inhibitor belumosudil. Sequential IC-Δ offers a robust, forward-looking pharmacovigilance framework that identifies adverse event acceleration 12–24 months before regulatory action. By emphasizing directional change and incorporating a simple confidence approximation, this approach enhances early signal detection in large safety datasets. Integration with electronic health records, regulatory pipelines, and interactive dashboards could further streamline horizon scanning and improve patient safety in GVHD prophylaxis."

Clinical • Bone Marrow Transplantation • CNS Disorders • Cytomegalovirus Infection • Dyslipidemia • Graft versus Host Disease • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Metabolic Disorders • Pneumonia • Rare Diseases • Respiratory Diseases • Septic Shock

Large language models extract diverse manifestations of chronic GVHD from unstructured clinical documentation (ASH 2025) - "Of these patients, 58 were steroid refractory/dependent and received a second line immunosuppressant such as ruxolitinib (76% of patients), belumosudil (14%), or ibrutinib (16%). Presence of any non-scorable symptom (i.e. muscle symptom, nasal/sinus symptoms, serositis, or capillary leak syndrome) in the two weeks leading up to the start of corticosteroid therapy occurred more frequently in patients who required additional immunosuppression (11/58, 19.0%) compared those who received prednisone alone (6/85, 7.1%) with an odds ratio of 0.32 (pvalue 0.04)...This approach enabled the construction of a comprehensive database of events post-transplant. We anticipate that this database will facilitate future investigation into distinct patterns of cGVHD activity, creating well-calibrated metrics of disease severity, and predicting response to immunosuppressive therapy."

Clinical • Cardiovascular • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Otorhinolaryngology

The safety and efficacy of belumosudil and ruxolitinib combination in ruxolitinib refractory chronic graft-versus-host disease (ASH 2025) - "High response rates (ORR 54.8%, best ORR 76.2%), durable disease control (12-month FFS 92.5%), and significant CS reduction (median 70.8% dose decrease) were achieved without severe toxicity (grade ≥3 infections: 4.8%; no treatment discontinuations). These findings support the mechanistic rationale for concurrent JAK/ROCK inhibition and warrant prospective validation."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Pneumonia • Respiratory Diseases

Real-world experience with ruxolitinib therapy for steroid-refractory acute graft-versus-host disease following umbilical cord blood transplantation (ASH 2025) - "GVHD prophylaxis consisted of tacrolimus (Tac) plus mycophenolate mofetil in 54 patients and Tac plus short-term methotrexate in 1. RUX therapy for SR-aGVHD following UCBT showed a meaningful response rate, with sustained benefit observed in responders. Although cytopenias and infections were frequently encountered, most patients were able to continue treatment. RUX may represent a viable treatment option for SR-aGVHD in the UCBT setting, with careful attention to adverse events."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Influenza • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • Transplantation

Belumosudil is effective in patients with chronic graft-versus-host disease lasting more than two years: A retrospective single-center real-world study (ASH 2025) - "Resistance to the most recent prior therapy (including glucocorticoid, calcineurin inhibitors, mycophenolate mofetil, ruxolitinib, mesenchymal stem cells, etc.) was observed in 82.4% (n = 14). This real-world study demonstrates that belumosudil is efficacious, well-tolerable, and safe for recipients with cGVHD persisting for at least 2 years after diagnosis and following multiple lines of anti-cGVHD therapy. Most patients exhibit meaningful clinical improvement with belumosudil. No significant increase in the risk of disease recurrence or infection was observed."

Real-world • Real-world evidence • Retrospective data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia

Conversion from calcineurin inhibitor to ruxolitinib as GVHD prophylaxis during patients with transplant-associated thrombotic microangiopathy (ASH 2025) - "Replacement of CNIs with ruxolitinib in patients with TA-TMA might be an acceptable alternative, and a multicenter confirmatory study of CNIs replacement with ruxolitinib is justified."

Clinical • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock • Transplantation

Incidence, predictors and consequences of poor graft function after post-transplant cyclophosphamide (PTCy)-based allogeneic transplantation (ASH 2025) - "Patients who had PGF were more likely to be CMV positive, ABO incompatible, had microangiopathic hemolytic anemia (MAHA), acute GVHD, or had been treated with ruxolitinib or sirolimus. Although PGF significantly increased the risk of NRM, it had no impact on survival due to a corresponding decrease in relapse incidence. The positive effect of PGF on relapse reduction, which is independent of disease-related factors or the development of CMV reactivation or GVHD, deserves further study to understand the basis of this finding."

Post-transplantation • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Transplantation

Prescribing patterns in MDS/MPN syndromes (ASH 2025) - "Additionally, the prescribing patterns of Hydroxyurea, Hypomethylating Agents (HMA)- Azacitidine/Decitabine and JAK inhibitors Ruxolitinib/Cedazuridine/Pacritinib/Momelotinib/Fedratinib were analyzed in these patients. In this real-world analysis, our data demonstrate that over 90% of patients diagnosed with MDS/MPN overlap syndromes do not receive any treatment in routine clinical practice. The most prescribed medication in this cohort of patients with MDS/MPN was hydroxyurea, followed by hypomethylating medications (decitabine and azacitidine). Being untreated was associated with a significant decrement in survival, with untreated patients having up to twice the risk of death than those treated."

Atypical Chronic Myeloid Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Myelodysplastic/myeloproliferative overlap neoplasms: Clinicopathological features, treatment strategies, and outcomes — a UK multicentre cohort Study (ASH 2025) - "29% had an antecedent diagnosis of MPN (n=18) or MDS (n=7), and 11 treated with either hydroxyurea (HU; n=9), anagrelide (ANA; n=3), hypomethylating agent (HMA; n=1) or underwent allogeneic transplantation (allo-HCT; n=1)...Treatment was initiated in 57%; 29 (33%) received HU, 7 (8%) ANA, 13 (15%) HMA, 6 (7%) ruxolitinib, and 5 underwent allo-HCT... MDS/MPN neoplasms present therapeutic challenges due to heterogenic phenotypes, lack of clear survival benefit with current non-transplant therapies, poor OS post allo-HCT and a paucity of new agents. Genomic characterisation aids prognostic estimation across all subtypes. Moreover, we confirm the prognostic relevance of 'genomically stratifying' the MDS/MPN-NOS group as per the seminal work of Paloma et al, aiding therapeutic decisions."

Clinical • Cardiovascular • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Thrombocytosis • Thrombosis • ASXL1 • JAK2 • RUNX1 • SETBP1 • SF3B1 • SRSF2 • STAG2 • TET2 • TP53

Clinical features and outcomes of myeloproliferative neoplasm patients with MPL mutations and concurrent JAK2/calr mutations (ASH 2025) - "ET treatments included hydroxyurea and off-label Ropeginterferon alfa-2b. Among those with MF, 7 patients received ruxolitinib, 2 required anemia-related therapies, including darbepoetin alfa and Luspatercept...However, further work is required to investigate this hypothesis. Limited follow-up and the predominance of White populations in our cohort underscore the need for studies involving larger and more diverse populations with extended longitudinal data to better understand the prognostic significance and therapeutic implications of the co-mutations."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • ASXL1 • CALR • JAK2 • NOTCH1 • SF3B1 • SH2B3 • SRSF2 • TET2

Phase 3 randomized double-blind study evaluating selinexor, an XPO1 inhibitor, plus ruxolitinib in jaki-naïve myelofibrosis: Study rationale and preliminary patient characteristics (ASH 2025) - P3 | "These preliminary patient characteristics demonstrate that the population enrolled to date is consistent with those enrolled in other major phase 3 studies of MF and representative of the intended population. Higher baseline TSS may lead to more robust improvements in Abs-TSS that can better assess impacts on symptom burden in heterogenous populations across disease severity than TSS50, which is less sensitive to changes and may miss clinically meaningful changes in symptoms. Results from SENTRY will provide important insights into the effects of SEL in combination with RUX and potential benefits across key subgroups in JAKi-naïve MF, a population with continued unmet need for therapies to improve splenomegaly, symptom control and address disease modification."

Clinical • IO biomarker • P3 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • CALR • JAK2

Indirect treatment comparison of novel JAK2 Inhibitor OB756 versus ruxolitinib in polycythaemia vera with splenomegaly (ASH 2025) - "Overall, OB756 appears to show potential benefits in efficacy and safety in PV patients with splenomegaly compared to ruxolitinib in preliminary analyses of RESPONSE-1 study. These findings suggest that OB756 may offer advantages in reducing both hematological AEs such as anemia, thrombocytopenia, lymphopenia, neutropenia, and non-hematological AEs in JAK inhibitor-naïve PV patients with splenomegaly. However, these observations require confirmation through direct head-to-head studies."

Leukopenia • Neutropenia • Polycythemia Vera • Pulmonary Disease • Thrombocytopenia

Extended validation of the RR6 prognostic model at 6 and 12 months in primary and secondary myelofibrosis patients treated with ruxolitinib (ASH 2025) - "RR6 enables early identification of high-risk patients after six months and retains its relevance at 12 months, supporting timely clinical decisions regarding therapy modification or transplant referral. Its use may enhance personalized treatment strategies in MF."

Clinical • Hematological Disorders • Myelofibrosis • ASXL1 • CALR • IDH2 • JAK2 • U2AF1

Interferon therapy achieves potent reduction in JAK2 allele burden in patients with myeloproliferative neoplasms: A real-world analysis (ASH 2025) - " This single center, retrospective study evaluated consecutive pts treated with pegylated interferon alfa-2a (peg-IFN) or ropeginterferon alfa-2b (ropeg), regardless of line of therapy...Prior therapy included hydroxyurea, anagrelide, and ruxolitinib in 36 (43.9%), 2 (2.4%), and 8 (9.8%) pts, respectively; 44 had not received prior cytoreductive therapy... This real-world analysis demonstrates the feasibility and efficacy of IFN therapy in clinical practice. Most pts achieved sustained CHR with low treatment discontinuation rate; thrombotic and disease progression events were rare. Importantly, we demonstrate the substantial impact of IFN on reducing JAK2 allele burden."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombocytosis • Thrombosis • JAK2 • NPM1

Real-world hematologic response and treatment patterns among patients with polycythemia vera (PV) treated with ropeginterferon alfa-2b (ropeg) (ASH 2025) - "While cytoreductive therapy, particularly hydroxyurea (HU), has been a mainstay treatment, ropeg has emerged as a promising new treatment approach based on recent trial results, subsequent FDA approval, and inclusion as a NCCN Guideline preferred treatment...Among 2L+ patients, prior therapies included HU (71%), ruxolitinib (25%), peginterferon alfa-2a (6%), and interferon alfa-2b (1%)...These findings support the effectiveness of ropeg in community practice populations and provide benchmarks for future studies. Further research, including abstraction of unstructured data, is warranted to explore more details on dosing, duration of therapy, adverse effects, driver mutations, allele burden declines, and long-term outcomes."

Clinical • Real-world • Real-world evidence • Chronic Eosinophilic Leukemia • Hematological Disorders • Myeloproliferative Neoplasm • Polycythemia Vera

Efficacy and safety of ruxolitinib-based combination therapy in the patients with myelofibrosis (MF): A systematic review and meta-analysis (ASH 2025) - "Among JAK inhibitor-naïve patients, the combination of ruxolitinib with selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by ruxolitinib plus BMS-986158 (SVR35: 90%). In addition, the efficacy ofthe combination of ruxolitinib with IFNα(SVR35:70%) and pelabresib (SVR35:66%; TSS50:53%) are also acceptable. For patients with prior JAK inhibitor exposure, ruxolitinib plus siremadlin (SVR35: 45%) and ruxolitinib plus selinexor (SVR35: 38%; TSS50: 33%) showed notable activity... For JAK inhibitor-naïve patients, ruxolitinib-based combination regimens demonstrated advantages over ruxolitinib monotherapy. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure."

Combination therapy • Retrospective data • Review • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Thrombocytopenia • IFNA1

Significant improvement of bone marrow fibrosis in patients with chronic myeloproliferative neoplasms (CMPN) treated with ruxolitinib. (ASH 2025) - "A very significant decrease in the grade of myelofibrosis was found, mainly in patients with thrombocythemia and polycythemia (68.7 %) and in 5 patients (31.3 %) there was no progression. Although the sample of patients is small, the results are encouraging. Studies with a larger number of patients are required."

Clinical • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis