T Cell Non-Hodgkin Lymphoma

P1, N=21, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2025 --> Dec 2025 | Trial primary completion date: Aug 2023 --> Dec 2024

Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL.

P3, N=80, Recruiting, Soligenix | Not yet recruiting --> Recruiting

P2, N=36, Recruiting, Yale University | Not yet recruiting --> Recruiting

P1, N=54, Recruiting, Washington University School of Medicine | Active, not recruiting --> Recruiting

Furthermore, specific inhibitory ligand-receptor interactions, such as CLEC2D-KLRB1, CTLA4-CD86, and MIF-CD74, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.

To the best of our knowledge, this is the first reported case of AITL with TCR::MYC rearrangement. This condition could be associated with refractoriness to chemotherapy and aggressive clinical course with systemic infiltration that included the intestine.

Based on specificity, efficacy, and loss of the target antigen, CARLY3 represents a potential novel CAR treatment for NHL.

Despite the notion that CIE might be a mere bundle of various yet uncharacterized disease processes, we found specific pathogenic signatures in these patients, that were different from other forms of erythroderma. These data might help to improve our pathogenic understanding of the blood and skin compartments of CIE, aiding in discovery of future treatment targets.

P1/2, N=40, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Feb 2025 --> Dec 2025 | Trial primary completion date: Feb 2025 --> Jun 2025

Many genetic abnormalities, mainly associated with the TCR signaling pathway, are observed, and most are more frequent in the aggressive type than in the indolent type, except for STAT3, indicating the heterogeneous pathogenic process of ATLL. In this review, we present the latest findings on molecular pathogenesis and histopathological findings of ATLL in the era of the new classification of lymphomas, serving as a basis for future research and classification.

Additionally, we found that PIK-75 oc-HDL NP, but not free PIK-75 or oc-HDL NP alone, reduced the IC50 in the NCI-60 cell line panel and additional pancreatic cancer cell lines. These data demonstrate the first example of drug-loaded oc-HDL NP that actively target SR-B1 and kill cancer cells in vitro and in vivo, encouraging further development and translation to human patients.

these findings underscore the promise of FoxP3+ cell quantities as added value in prognosis and highlight the potential benefits of Treg-stimulating therapies in PTCLs.

First, our findings suggest that S. aureus with its virulence factor spa fuels MF progression through non-canonical NF-κB and IL-1B signalling. Second, our data provide insights into the potential role of viruses in MF aetiology. Last, we propose a model of microbiome-driven MF aetiopathogenesis: Thymocytes undergo initial oncologic transformation, potentially caused by viruses. After maturation and skin infiltration, an outgrowing, pathogenic S. aureus strain evokes activation and maturation into effector memory T cells, resulting in aggressive disease. Further studies are warranted to verify and extend our data, which are based on computational analyses.

It remains uncertain if nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and EBV-positive T/NK-cell lymphoproliferative diseases.

The AUC values of GNLY and FYB1 were 0.86 and 0.79, respectively. In conclusion, GNLY and FYB1 can be promising diagnostic biomarkers for differentiating early-stage MF from psoriasis and chronic spongiotic dermatitis.

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

Despite its rarity, scant information is available about double-negative mycosis fungoides, with only a limited number of cases documented in the existing literature. This review aims to provide enhanced clarity, comprehension, and a detailed exploration of the spectrum encompassing double-negative mycosis fungoides.

P1, N=50, Not yet recruiting, Treeline Biosciences, Inc.

P2, N=19, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P1, N=10, Recruiting, Wuhan Union Hospital, China

Moreover, hyperacetylation of GAPDH was confirmed in human PTCL patient samples containing the VAV1-MYO1F gene fusion. Overall, this study revealed not only the mechanisms by which MYO1F regulates T-cell metabolism and VAV1-MYO1F fusion-induced PTCL but also promising therapeutic targets for the treatment of PTCL.

He was initially diagnosed as donor-derived myelodysplastic syndrome (MDS) and treated with azacitidine, followed by secondary transplantation using unrelated BM, providing durable complete remission...DC-TAM is a rare UCBT-related complication which resembles MDS, but the identification of GATA1 mutation may be useful for its diagnosis. Our genetic analyses revealed that a pre-existing clone in UCB may contribute to the development of donor cell-derived hematologic neoplasms, highlighting the potential relevance of genetic screening of donor UCB.

We developed a Type 2/17 immune signature classifier based on cytokine profiling, which showed that cases of erythroderma fall within distinct categories of immune activation. This categorization may have utility in guiding clinical decisions.

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

Our proposed diagnostic features are statistically valid and, along with those previously reported, can aid in identifying and distinguishing MF cases from MF-mimicking cases.

Using complementary genetically engineered mouse (GEM) models, we demonstrated that TP53 and/or PTEN deficient TCL, and LAM within their TME, are sensitive to the selective XPO1 antagonist selinexor...We identified a novel role for eIF4E/XPO1 in exporting GATA-3 and GATA-3-dependent transcripts from the nucleus in TCL, and in the export of therapeutically relevant transcripts, including CSF-1R, from LAM. Therefore, XPO1 antagonism, by impairing oncogenic transcriptional programs in TCL and depleting LAM from their TME, is a novel approach to target two independent dependencies in a group of therapeutically challenging TCL.

P1/2, N=89, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Oct 2026 --> Feb 2026

P3, N=294, Not yet recruiting, Eastern Cooperative Oncology Group

P2, N=46, Active, not recruiting, University College, London | Trial completion date: Sep 2024 --> Sep 2025

P1/2, N=11, Completed, Mayo Clinic | Active, not recruiting --> Completed

In addition, there were significant differences in the levels of five individual metabolites based on the univariate statistical analysis. Our results showed alterations in energy, protein and lipid metabolism, suggesting glucose, lactate, N-acetyl glycoproteins (NAGs), scyllo-inositol and choline as possible new candidate biomarkers in canine multicentric lymphoma.

In contrast to MF/SS, PCAETCL and PCGDTCL remain diseases with few prospective studies to guide treatment. However, recent genomic insights on these diseases, such as the presence of JAK2 fusions in PCAETCL and cell of origin findings in PCGDTCL, have created options for new biomarker-driven strategies.

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.

Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

CDK9 also promotes degradation of retinoic acid receptor α (RARα) via recruiting the E3 ligase HUWE1. Co-administration of CDK9-PROTAC (GT-02897) with all-trans retinoic acid (ATRA) leads to synergistic attenuation of tumor growth in vitro and in xenograft models, providing a potential translational treatment for complete eradication of CTCL.

The probiotics showed positive effects on urinary symptoms in HTLV-1-associated myelopathy/tropical spastic paraparesis patients but did not significantly impact other clinical or paraclinical parameters within the 12-week study period. These findings suggest that probiotics may offer symptomatic relief for some symptoms of HTLV-1-associated myelopathy/tropical spastic paraparesis patients.

P=N/A, N=26, Completed, Takeda | Recruiting --> Completed | N=50 --> 26

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

In order to gain insight on the TET mediated molecular events that safeguard T cells from aberrant proliferation we performed serial adoptive transfers of murine CD4 T cells that lack concomitantly TET2 and TET3 to fully immunocompetent congenic mice. Here we show a progressive acquisition of malignant traits upon loss of TET2 and TET3 that is characterized by loss of genomic integrity, acquisition of aneuploidy and upregulation of the protooncogene Myc.

The utilization of various B-cell markers in combination could aid pathologists in distinguishing between various stages of B-cell maturation, assessing tumor cell heterogeneity, and determining the phenotype in scenarios where there is a loss of common B-cell markers diffuse large B-cell lymphomas is the most prevalent subtype of feline lymphoma. Significantly, relying solely on immunochemistry with one parameter may not be sufficient for a definitive diagnosis of B-cell lymphoma, as another parameter may also be necessary.

We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation. Both JPX-0700/-0750 treatment reduced leukemic cell growth in human AML or NKCL xenograft mouse models significantly, being well tolerated by mice. Synergistic cell death was induced upon combinatorial use with approved chemotherapeutics in AML/NKCL cells.