Jakafi (ruxolitinib)

Ruxolitinib-based regimens, administered in 19 patients (40%) as EMH-directed therapy, yielded rapid palliation (dyspnea/ascites resolution), complemented by radiotherapy (11%) and splenectomy; HSCT achieved complete remission in one case...Atypical EMH signals advanced myelofibrosis with dismal prognosis, responsive to JAK inhibitors/locoregional therapies but highlighting sanctuary biology. Systematic surveillance and transplant referral are imperative; prospective registries are needed to refine risk models and test novel antifibrotics.

P2, N=29, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jun 2026 --> May 2027

In this evidence-based review, we trace the evolution of risk stratification in PV and ET and examine the clinical evidence supporting current cytoreductive options, specifically hydroxyurea, interferons, ruxolitinib, and anagrelide. We argue for a paradigm shift away from binarily driven thrombosis-centric risk stratification toward a personalized, proactive approach that integrates molecular and inflammatory biomarkers, expands the population offered cytoreduction, and prioritizes disease-modifying therapies. Prospective studies are needed to validate the incorporation of these markers into risk-adapted algorithms and to define the long-term impact of early disease modification on transformation, survival, and quality of life.

Concomitant use of CYP3A4-interacting agents (e.g., ruxolitinib) was not associated with increased toxicity or isavuconazole level alterations. In this retrospective cohort of high-risk pediatric hematology patients, isavuconazole used as primary antifungal prophylaxis showed favorable safety, consistent drug exposure, and no breakthrough IFDs. These findings support further prospective evaluation of isavuconazole in pediatric prophylactic strategies.

P2, N=18, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; The decision to close the study was made due to the expiration of remaining drug supply.

Here we show calcium/calmodulin-dependent protein kinase II gamma (CaMKII-γ) regulates bortezomib-resistant MM (BRMM) via AMPK-ULK1-autophagy axis. High-throughput screening identified ruxolitinib as a selective CaMKII-γ inhibitor, which reverses BRMM resistance in vitro (using U266 and KMS11 bortezomib-resistant cell lines) and in vivo (using female BALB/c nude mouse model), with efficacy comparable to genetic CaMKII-γ ablation, providing a potential therapeutic strategy for BRMM with broader implications to improve patient outcomes in the future.

P2, N=112, Active, not recruiting, Incyte Corporation | Trial completion date: Sep 2027 --> Nov 2026 | Trial primary completion date: Sep 2027 --> Nov 2026

Collectively, these findings establish HIF-1-driven glucose metabolism as a metabolic vulnerability in JAK2V617F-positive MPN. The selective exhaustion of patient-derived clones defines the HIF-1-GLUT1/3 axis as a central, targetable bottleneck. These data provide a mechanistic rationale for further investigation of HIF-1 or GLUT inhibitors, suggesting that targeting this fundamental requirement may help overcome clinical limitations to achieve disease modification and eradicate the malignant clone.

In clinical practice, ruxolitinib exposure shows substantial variability and is strongly affected by strong CYP inhibitors that are frequently co-administered. Whilst no clear exposure-efficacy relationship was observed, higher exposure was linked to increased toxicity risk, arguing for careful dose adjustment.

Apart from treating promptly the underlying trigger conditions, earlier incorporation of targeted anti-cytokine therapy such as anakinra is strongly favored these days. The cytotoxic etoposide shall be chiefly reserved for malignancy-associated HLH, including B-cell lymphomas, and refractory disease. Rituximab has led to superior outcomes when utilized to clear EBV-infected B-cell reservoirs...The anti-IFN-γ monoclonal antibody emapalumab has been approved for refractory HLH cases. The JAK 1/2 inhibitor ruxolitinib may prove useful in this space as well. The therapeutic arsenal is likely to evolve further in the direction of agents addressing specific pathophysiologic steps in asHLH. Targeting effector cytokines, their receptors, inflammasome pathways are promising future directions in asHLH therapeutics.

P1, N=24, Recruiting, Stanford University | Trial primary completion date: May 2026 --> Dec 2026

P3, N=340, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting