Cutaneous T-cell Lymphoma

Here we report a case of radiation-induced cSCC with a high level of tumor-mutation burden that developed in a patient with MF who was successfully treated with pembrolizumab. The present case suggests that pembrolizumab might be an optimal therapy for radiation-induced cSCC, even at advanced stages.

In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

P1, N=21, Recruiting, Baylor College of Medicine | Trial completion date: May 2039 --> May 2040 | Trial primary completion date: May 2024 --> May 2025

PEG IFN α-2a for MF/SS showed ORR of 53%, TTNT of 9.2 months, superiority of combination regimens in comparison to monotherapy and doses of 180 mcg/weekly related to higher ORR.

P2, N=30, Active, not recruiting, Northwestern University | Trial completion date: Aug 2023 --> Aug 2024

Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort.

This study underscores the complexities in distinguishing eMF from inflammatory skin diseases, advocating for a comprehensive diagnostic approach.

CD39 was overexpressed by peripheral blood T-cells in Sezary syndrome and mycosis fungoides, and in skin-infiltrating lymphocytes of Sezary syndrome, mycosis fungoides, subcutaneous panniculitis-like T-cell lymphoma and primary cutaneous CD30-positive lymphoproliferation. Our study emphasizes the interest in using CD39/CD73/adenosine pathway blocking agents for cutaneous T cell lymphomas treatment.

P1, N=20, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

P1, N=49, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

This is especially intriguing as malignant T cells in CTCL develop from CD4 + T cells. Hence, CuV should be further investigated for the overall role it plays in the complex tumor microenvironment of CTCL/MF.

The presence of genetic variations in one or more TRM functional gene may predispose patients to develop MF. Further studies involving a larger patient population and a comparative analysis of protein expression will be necessary to validate these findings.

Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well.

No abstract available

P1, N=120, Recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Apr 2032 | Trial primary completion date: Dec 2024 --> Dec 2028

Our case series, the largest international cohort of γδ T cell predominant LyP cases, confirms marked clinicopathologic heterogeneity that may contribute to misdiagnosis, reasserting the need to identify classic clinical features, CD30+ T-cell components, and markers of cytotoxicity when dealing with this differential diagnosis. A limitation of this study includes somewhat limited follow-up, histologic, and immunophenotypic information for some cases.

Fourteen patients with known GVHD underwent transplantation between 50 and 365 days after their last dose of mogamulizumab, while 2 underwent transplantation within 50 days after treatment. Based on this limited evidence, GVHD was not associated with the time interval from last mogamulizumab dose to transplantation.

By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.

P=N/A, N=12, Recruiting, Leiden University Medical Center | Trial completion date: Jun 2023 --> Mar 2025 | Trial primary completion date: Jun 2023 --> Mar 2025

While the 2022 ICC introduced the term "primary cutaneous marginal zone LPD," in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.

P1, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.

No abstract available

Importantly, residual CD4+ T cells following Sézary cell ablation lacked any immunologic shifts. These findings collectively unveil an auxiliary role for augmenting monocytic activity during mogamulizumab therapy in the treatment of SS and underscore the importance of targeted combination therapy in this disease.

If persistent or generalized purpuric lesions are present, PPD-like MF should be taken into consideration. A thorough physical examination combined with pathological findings may lead to a correct diagnosis.

P2, N=36, Not yet recruiting, Yale University | Initiation date: Jan 2024 --> Jun 2024

P1, N=6, Completed, Marcela V. Maus, M.D.,Ph.D. | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024

P1, N=25, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, Northwestern University | Trial completion date: Apr 2024 --> Dec 2026 | Trial primary completion date: Nov 2023 --> Dec 2026

Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8+ necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology.

P1, N=37, Active, not recruiting, National Cancer Institute (NCI)

P1/2, N=13, Active, not recruiting, City of Hope Medical Center | Trial primary completion date: Jun 2024 --> May 2023

P1, N=64, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P=N/A, N=50, Recruiting, Takeda | Not yet recruiting --> Recruiting

Our data support predictive validity of prognostic factors and models in MF and identified further potential parameters associated with poor survival. Prospective studies on prognostic indices across disease stages and treatment modalities are needed to predict and improve survival.

Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia.

There appears to be a relationship between cutaneous T-cell lymphoma and the cutaneous and intestinal microbiome, as well as a possible pathophysiological pathway involved. The possible modulation of the cutaneous and intestinal microbiome or the action on the signaling inflammatory pathway, using pharmacological tools such as JAK inhibitors or IL-17 inhibitors in the latter case, could open the possibility for future therapeutic studies for cutaneous T-cell lymphoma.

P1, N=21, Active, not recruiting, National Cancer Institute (NCI) | N=38 --> 21 | Trial completion date: Dec 2023 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Aug 2023

While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.

No abstract available