Peripheral T-cell Lymphoma

However, rare cases of T-ALL expressing bright CD45 and lacking expression of immature markers can be a diagnostic conundrum and difficult to differentiate from mature T-cell lymphomas lacking surface CD3 expression or aberrantly expressing immature markers, which affects treatment decisions and prognosis. Here, we summarize the clinical, pathologic, and genetic features of 3 pediatric T-ALL cases with an entirely mature immunophenotype.

Taken together, our findings firstly identified that targeting PTGDS promotes the ferroptosis in PTCL through regulating HMOX1-mediated iron metabolism, and highlighted novel therapeutic strategies to improve the efficacy of ferroptosis-targeted therapy in PTCL patients.

P1/2, N=130, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Jul 2029 | Trial primary completion date: Mar 2025 --> Jul 2024

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

P1/2, N=130, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

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

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.

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.

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.

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.

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.

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.

P=N/A, N=1006, Completed, Takeda | Active, not recruiting --> Completed | N=2800 --> 1006 | Trial completion date: Dec 2024 --> Jul 2024 | Trial primary completion date: Dec 2024 --> Jul 2024

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

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.

P1/2, N=230, Active, not recruiting, Taiho Oncology, Inc. | Trial completion date: Oct 2024 --> Dec 2025

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=33, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Such compounds hold the potential of improving the pharmacokinetic and pharmacodynamic profiles of HDAC inhibitors through the extension of the drug-target residence time. This perspective aims to capture this emerging paradigm and discuss its potential to improve the preclinical/clinical outlook of HDAC inhibitors in the coming years.

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

The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK-high group, which had more frequent copy number changes and was enriched with pathways associated with cell growth, proliferation, and metabolism. Altogether, these findings suggest that there is molecular heterogeneity within pediatric ALK+ ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.

The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. Somatic DNMT3A and TET2 mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant. The PTCL harbored an additional somatic TET2 mutation, which was already detectable in the CAR T-cell apheresis product and the final CAR T-cell product at very low frequencies, providing evidence that clonal hematopoiesis had contributed to lymphomagenesis.

P2, N=50, Not yet recruiting, Evopoint Biosciences Inc.

This review aims to provide a comprehensive overview of AITL, including its clinical presentation, epidemiology, pathogenesis, histomorphology and treatment options. Despite advancements in the understanding of AITL biology and the development of novel treatment strategies, the prognosis for patients with AITL remains poor.

The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic natural killer cells.

P2, N=51, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

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

The PTCL-TFH cases correlated with an angioimmunoblastic T-cell lymphoma (AITL) gene signature, had more EBER-positive cells than the PTCL-GATA3 and PTCL-TBX21 cases, and a subset had some morphologic features of AITL (p < 0.01). This study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and should enable more precise diagnosis and tailored therapeutic strategies in the future.

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

P=N/A, N=25, Not yet recruiting, Peking University People's Hospital

The safety profile of valemetostat monotherapy was acceptable in these patients with relapsed or refractory non-Hodgkin lymphoma. Favourable clinical activity was observed. These findings support a new indication for valemetostat in this setting.

These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile.

we report the first case of EMS with t(1;8)(q25;p11) to have a favorable outcome after allo-HSCT. The encouraging results support the use of aggressive chemotherapy in conjunction with early allo-HSCT for EMS patients with t(1;8)(q25;p11).

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

P1/2, N=18, Completed, University of Colorado, Denver | Active, not recruiting --> Completed

No abstract available

P3, N=150, Recruiting, Corvus Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting