Cutaneous T-cell Lymphoma

P1, N=24, Recruiting, SIRPant Immunotherapeutics, Inc. | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Mar 2025 --> Jun 2025

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

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.

The patient's condition deteriorated, and she died during her hospitalization. This case reviews the clinicopathologic findings of pcALCL, emphasizes the importance of clinicopathologic correlation in differentiating between CD30+ lymphoproliferative disorders, highlights the extremely rare phenomenon of systemic intramuscular and visceral disseminated disease occurring in pcALCL, and discusses implications for prognosis.

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.

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.

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.

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.

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.

Using a cut-off set at 30% expression of neoplastic cells, we noted an overexpression of p53 in T-MF and T-SS compared with nontransformed forms (47% vs. 12%, respectively, P < 0.01) and in MF compared with SS (23% vs. 7%, respectively, P < 0.01). Overexpression of p53 with a cut-off at 30% therefore seems to be a discriminating tool in the differential diagnosis of MF/SS versus their transformed forms as well as the differential diagnosis between MF and SS.

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.

P2, N=9, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Oct 2024

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

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.

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.

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

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

In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development.

P1, N=46, Not yet recruiting, Mayo Clinic

P1, N=18, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting | N=110 --> 18

VAV1 silencing induces apoptosis and inhibits cell growth, which is associated with upregulation of Bcl-2 modifying factor and downregulation of bone morphogenetic proteins and activin membrane-bound inhibitor. Therefore, VAV1 may be a potential tumour marker and therapeutic target for CTCLs.

Neutrophil-lymphocyte-ratio, pan-inflammation-value, CD30 positivity, Ki-67 index, large cell transformation, and monoclonal T-cell receptor gene rearrangement were not associated with prognosis. In conclusion, MTBI is useful and promising prognostic marker for tumor-stage MF.

P=N/A, N=20, Recruiting, Centre Hospitalier Universitaire de Besancon | Trial completion date: Jul 2023 --> Jul 2025 | Trial primary completion date: Jul 2023 --> Jul 2025

P2, N=20, Not yet recruiting, M.D. Anderson Cancer Center

Thanks to international cooperative groups, treatment of mycosis fungoides, CD30+ lymphoproliferations and erythrodermic lymphomas is now well established which is not the case for the other entities. Treatments may be classified in five categories: skin directed therapies, systemic non-chemotherapeutic treatments, immunomodulators, targeted immunotherapies and chemotherapies.

It was administered treatment based on prednisone and phototherapy with a good response. This case makes possible an outlook of the demographic data of HMF, and it allows this entity to be taken into consideration for possible differential diagnoses that are not contemplated due to the limited dissemination of knowledge about this disease. It is important to emphasize the knowledge of HMF since early diagnosis and timely treatment will improve the prognosis in our patients and prevent them from being treated incorrectly.

P2, N=9, Active, not recruiting, Mayo Clinic | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=170, Active, not recruiting, Innate Pharma | Trial completion date: Oct 2024 --> Jan 2026

P2, N=82, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

In 5 patients with PTCL, ctDNA negativity showed 100% concordance with negative PET-CT results. Our results, albeit with small numbers, suggest that ctDNA is strongly associated with clinical outcomes in patients with PTCL; ctDNA may serve as a useful tool to monitor and prognosticate patients with PTCL when validated in a large cohort of patients.

P1/2, N=40, Completed, Nanjing Zenshine Pharmaceuticals | Recruiting --> Completed | N=70 --> 40

Because the disease is indolent, aggressive diagnostic tests and systemic treatments are not recommended. We present a case of PCSM-LPD in a previously healthy young man that spontaneously regressed after a biopsy.

P1, N=120, Active, not recruiting, Kymera Therapeutics, Inc. | Recruiting --> Active, not recruiting

P2, N=26, Active, not recruiting, John Reneau | Trial completion date: Apr 2024 --> May 2025 | Trial primary completion date: Apr 2024 --> May 2025

P=N/A, N=15, Not yet recruiting, Northwestern University

P1/2, N=40, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Aug 2040 --> Aug 2038 | Trial primary completion date: Aug 2025 --> Sep 2027

P1, N=23, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=10 --> 23 | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

Statin discontinuation led to complete symptom resolution, emphasizing the reversibility of drug-induced T-cell dyscrasia. This case highlights the importance of a detailed medication history as drug-induced T-cell dyscrasia, unlike classic CTCD with its characteristic lymphoid atypia, phenotypic abnormalities, and clonality leading to a refractory course, can be reversed by drug withdrawal.