P4, N=50, Not yet recruiting, Wake Forest University Health Sciences

Upadacitinib is an oral selective Janus kinase 1 (JAK1) inhibitor that targets specific pathways in immune-inflammatory responses. The patient achieved complete remission following standard induction therapy with all-trans retinoic acid and arsenic trioxide, with an uneventful treatment course. Notably, this clinical presentation markedly differs from typical APL cases, demonstrating unique biological characteristics.

P1/2, N=156, Recruiting, Hangzhou Highlightll Pharmaceutical Co., Ltd | Not yet recruiting --> Recruiting

We have further summarized clinical pharmacological interventions for such cardiotoxicity, including interleukin (IL)-6 receptor antagonists (tocilizumab), interferon-γ inhibitors (emapalumab), and Janus kinase inhibitors (ruxolitinib). These findings provide novel directions and drug candidates for the treatment of CAR-T cell therapy-induced myocardial toxicity. This review provides a comprehensive theoretical basis for optimizing cardiovascular safety management and developing novel targeted interventions for CAR-T cell therapy.

P4, N=296, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting | Trial completion date: Sep 2027 --> Apr 2032

In recent years, oral therapy with the JAK1/2 inhibitor ruxolitinib has become the standard of care. Since 2021, the JAK2/FLT3 inhibitor fedratinib has also been approved in the EU (note: in Switzerland, fedratinib will no longer be available as of February 28, 2025, as Swissmedic did not extend its time-limited approval)...Compared to the other two JAK inhibitors, momelotinib is particularly effective in patients with clinically symptomatic moderate to severe anemia. Results from studies investigating additional JAK inhibitors, combination therapies, and novel agents have also demonstrated significant efficacy and point toward future therapeutic developments, although these approaches are not yet available for routine clinical practice.

Patients with specific chimeric RNAs, such as BRAF and JAK2, exhibited favorable responses to trametinib or ruxolitinib, and those with more neoantigens may benefit from immunotherapy. In subcutaneous xenograft models, tumors bearing Ctsc-Rab38 responded better to anti-PD1 therapy, highlighting its potential as a biomarker and therapeutic target. These findings indicate that chimeric RNAs can produce novel fusion proteins and neoantigens, disrupt the expression and function of partner genes, and guide clinical treatment stratification in ESCC.

Selinexor combined with azacitidine or ruxolitinib showed encouraging efficacy with a manageable safety profile in patients with MDS/MPN.

The cytotoxic and antifibrotic effects of the BCL-XL inhibitor ABT-263 (navitoclax), alone or combined with the JAK2 inhibitor ruxolitinib, were evaluated in stromal and hematopoietic contexts. Combined inhibition of BCL-XL and JAK2 produced synergistic antifibrotic and pro-apoptotic effects in MSCs, post-MPN acute myeloid leukemia (AML) cell lines, and patient-derived cells resistant to ruxolitinib. Collectively, these findings identified BCL-XL as a key mediator of MPN-associated fibrosis and therapeutic resistance, and confirmed dual targeting of BCL-XL and JAK2 as a rational strategy for advanced MPN.

CONCLUSIONS Patients with PV treated with ruxolitinib can develop active tuberculosis, including disseminated forms. When tumor markers are elevated and imaging reveals lesions suggestive of metastases, clinicians should include disseminated tuberculosis in the differential diagnosis and pursue histopathological and microbiological investigations to enable timely diagnosis and appropriate treatment.

Emapalumab, alemtuzumab and ruxolitinib show promising results, however widespread use is limited by small, non-randomized trials in a heterogenous population. Further international collaborative efforts to develop clinical trials to put conventional chemotherapy treatments head-to-head with these newer therapies is critical for advancement of these agents.

Importantly, co-administration of ruxolitinib, a clinically approved JAK1/2 inhibitor, dampened IFN-β signaling and rescued mice from lethal toxicity. Collectively, these findings define the pathophysiological consequences of sustained systemic IFN-β exposure and identify ruxolitinib as a potential mitigation strategy to manage IFN-β-mediated toxicity during OV treatment.