P1, N=30, Recruiting, Oncotherapeutics | Not yet recruiting --> Recruiting | Initiation date: Jan 2024 --> Dec 2022

These include new JAK inhibitors with greater specificity for JAK2, as well as "add-on" medications designed to enhance the effectiveness of ruxolitinib, in both patients who are new to the drug and in those who have shown suboptimal responses. Additionally, there is ongoing exploration of novel therapeutic targets. In this review, we will explore the immunotherapy approaches that are currently used in clinical practice for MPNs, as well as emerging strategies that are likely to change the treatment of these diseases in the coming years.

Summarized are traditional approaches to anemia management and the clinical trial efficacy and safety data that support momelotinib as an option in each setting from mild to severe anemia, including in the context of co-occurring thrombocytopenia. With the availability of momelotinib and other emerging therapies directed at anemia control, early treatment of anemia to avoid progression and support improvement in eligible patients with myelofibrosis should be a primary consideration.

Upon ruxolitinib withdrawal, TSLPRCART functionality recovered in vivo with clearance of subsequent ALL rechallenge. These translational studies demonstrate an effective two-pronged therapeutic strategy that mitigates acute CART-induced hyperinflammation and provides potential anti-leukemia 'maintenance' relapse prevention for CRLF2-rearranged Ph-like and DS-ALL.

Finally, disease hallmarks in MPL W515L -transplanted mice were attenuated upon treatment with the autophagy inhibitor hydroxychloroquine or the ROCK inhibitor Y27632, either as monotherapy or in combination with the JAK2 inhibitor ruxolitinib. Overall, our data indicate that aberrant cytokine secretion is dependent on secretory autophagy downstream of RhoA, targeting of which represents a novel therapeutic avenue in the treatment of myelofibrosis. TGFβ1 is released from megakaryocytes via RhoA-mediated secretory autophagy, and targeting this process can alleviate fibrosis progression in a preclinical mouse model of myelofibrosis.

P1/2, N=1, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Recruiting --> Active, not recruiting

Filgotinib significantly impacted circulating biomarkers related to UC pathology. Several proinflammatory and neutrophil activation biomarkers may be early mediators of filgotinib treatment effects.

P2, N=47, Not yet recruiting, Sun Yat-sen University

P3, N=614, Active, not recruiting, AbbVie | Enrolling by invitation --> Active, not recruiting

P3, N=609, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting

P2, N=27, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Apr 2025

P2, N=136, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting

P1, N=56, Completed, AstraZeneca | Active, not recruiting --> Completed

P1, N=28, Not yet recruiting, AstraZeneca

P2, N=40, Not yet recruiting, Fudan University

P3, N=315, Active, not recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Recruiting --> Active, not recruiting | N=210 --> 315 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

Anti-MDA5-positive DM was diagnosed, and she was treated with triple therapy combined with tofacitinib because poor prognostic factors existed...Subsequent antibiotic therapy resolved both the cutaneous and pulmonary lesions. This case highlights the importance of considering bacteremia and performing blood cultures when DM-related skin ulcers resist conventional treatments, even without fever during immunosuppressive therapy.

P3, N=438, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=32, Completed, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Recruiting --> Completed | Trial completion date: Oct 2024 --> Jun 2024

P2, N=91, Completed, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Active, not recruiting --> Completed

Anemia and interstitial pneumonia both significantly improved following treatment with a Janus kinase 2 gene inhibitor. In this report, we discuss the possible mechanisms underlying PMF complicated with ILD.

P2, N=90, Completed, Peking Union Medical College Hospital | Active, not recruiting --> Completed

Mechanistically, H19 competitively binds to the mRNA of YTHDC1 with MiR-107, and also interacts with the YTHDC1 protein, regulating the stability of SRSF1 and thereby affecting the alternative splicing of IL-6 and IL-10. Utilizing organoids and the patient-derived xenograft (PDX) model, it is found that ruxolitinib may represent a promising treatment option for PDAC patients with high H19 expression.

P3, N=480, Not yet recruiting, Jiangsu vcare pharmaceutical technology co., LTD

These include single-agent brentuximab vedotin, histone deacetylase inhibitors, duvelisib, ruxolitinib, EZH2 inhibitors, and azacitidine, among others. Follicular helper T-cell lymphomas, given frequent mutations in epigenetic regulator genes, may preferentially respond to agents such as histone deacetylase inhibitors, EZH2 inhibitors, and hypomethylating agents. As these therapies evolve in their use for both relapsed/refractory disease and then into frontline treatment, subtype-specific therapy will likely help personalize care for patients with PTCL.

P2, N=115, Completed, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Completed | Trial completion date: Dec 2025 --> Dec 2024

Regardless of baseline BMI category, efficacy was greater with tofacitinib versus placebo in patients with AS, and no treatment effect differences between categories were observed, with exceptions for BMI ≥ 30 kg/m2 (more active/treatment-refractory disease and a smaller sample size). Overall, tofacitinib safety was generally comparable across categories; however, AE/SAE rates with tofacitinib were higher in the BMI < 25 kg/m2 category (which had more current smokers). This post hoc analysis demonstrates that tofacitinib can be considered as a treatment option for AS, regardless of baseline BMI category; however, interpretation was limited by small sample sizes and differences in sample sizes and baseline characteristics across categories.

P2/3, N=20, Recruiting, Hospital Authority, Hong Kong

P4, N=214, Recruiting, Sixth Affiliated Hospital, Sun Yat-sen University | Not yet recruiting --> Recruiting

P2, N=48, Recruiting, Institute of Hematology & Blood Diseases Hospital, China

Currently there are five selective SMIs available in the United States with demonstrated efficacy for HS in clinical studies including apremilast, topical ruxolitinib, upadacitinib, fostamatinib, and sirolimus. These selective SMIs target four pathways hypothesized to be important to HS pathogenesis including phosphodiestase 4, Janus kinases, spleen tyrosine kinase, and mammalian target of rapamycin. Several new SMIs are currently in the clinical trial pipeline targeting Bruton's tyrosine kinase, aryl hydrocarbon receptors, heat shock protein 90 as well as interleukin-1 and -17 signaling pathways.

P1, N=56, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

P2, N=91, Completed, St Vincent's Institute of Medical Research | Active, not recruiting --> Completed

P=N/A, N=678, Recruiting, AbbVie

P4, N=150, Recruiting, Eisai Korea Inc. | Not yet recruiting --> Recruiting

P3, N=180, Recruiting, Incyte Corporation | Not yet recruiting --> Recruiting

P2, N=24, Recruiting, Milton S. Hershey Medical Center | Trial completion date: Jan 2025 --> Jan 2028 | Trial primary completion date: Oct 2024 --> Oct 2026

In fact, the use of selective JAK1 inhibitors ruxolitinib or baricitinib inhibited the induction of ISG's and the proliferation of p53 and ARF deleted cells. We identify a group of solid human tumors that lack functional p53 and ARF, show an expression signature of the upregulated type I IFN response genes, and are sensitive to selective JAK1 inhibitors. These data suggest that the type I IFN response acts as a positive driver of proliferation in the absence of p53 and ARF and, as such, presents itself as a potential therapeutic target in aggressive solid tumors.

Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment.

P3, N=241, Active, not recruiting, Priovant Therapeutics, Inc. | Trial completion date: Dec 2024 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Jul 2025

P3, N=642, Completed, AbbVie | Active, not recruiting --> Completed