Peripheral T-cell Lymphoma

Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In-depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.

Three cases previously classified as PTCL CD30+CD15+ showed DUSP22/IRF4 rearrangements, favouring a diagnosis of ALCL, ALK-. Our results suggest that cases previously designated PTCL CD30+CD15+, likely fall within the spectrum of ALCL, ALK-; additionally, a subset of ALCL, ALK- with DUSP22/IRF4 rearrangement expresses CD15, consistent with previous reports and expands the immunophenotypic spectrum of this lymphoma subgroup.

EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

P=N/A, N=50, Recruiting, University of Aarhus

P2, N=148, Active, not recruiting, Daiichi Sankyo | Trial completion date: Sep 2025 --> Apr 2028

P1/2, N=97, Recruiting, Antengene Corporation | Trial primary completion date: Dec 2023 --> May 2024

Localized treatment with frequent monitoring may be sufficient in ALK-positive pcALCL until there is evidence of progression. Physicians should be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK positivity and disease with skin recurrence.

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

P3, N=107, Recruiting, Peking Union Medical College Hospital | Not yet recruiting --> Recruiting | Trial primary completion date: Oct 2023 --> May 2024

Outcomes in mature T-cell lymphomas remain poor, with previous attempts at developing monoclonal antibodies (mAb) compromised by limited efficacy and significant immunocompromise. Anti-killer cell lectin-like receptor G1 mAbs may have greater selectivity and specificity for malignant T-cells and avoid the toxicity concerns with previous agents.

P1/2, N=132, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

However, ascites did not improve when treated with micafungin for Candida peritonitis. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.

Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.

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

P1, N=20, Completed, Innate Pharma | Active, not recruiting --> Completed | N=40 --> 20 | Trial completion date: Jul 2024 --> Feb 2024

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.

P1/2, N=130, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2024 --> Mar 2025

In conclusion, our data suggest that HBI-8000 inhibits fibrosis by modulating the TGF-β1/MAPK pathway thereby improving HFpEF. Therefore, HBI-8000 may become a new hope for the treatment of HFpEF patients.

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

P2, N=4, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed

Our study revealed that the expression of specific genes, including TNFRSF1B, TRADD2, and MAP3K7, may play an important role in chemotherapy resistance in peripheral T-cell lymphoma. Moreover, we identified the downregulation of the TNF signaling pathway, a crucial pathway involved in cell survival, death, and differentiation, as a potential contributor to the development of chemotherapy resistance in peripheral T-cell lymphoma. These findings provide valuable insights into the molecular mechanisms underlying chemotherapy resistance and highlight potential targets for overcoming treatment resistance in this challenging disease.

These hepatic impairment effects reduced between-subject variability by only 5%-8% for their respective parameter, with a large amount of remaining unexplained variability. With further validation, this model can be leveraged to assess the need for dose adjustments in this patient population.

P1, N=38, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=63 --> 38 | Recruiting --> Terminated | Trial primary completion date: Mar 2022 --> Jun 2023; The sponsor has adjusted its R&D strategy.

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

P2, N=52, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2024

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

The 3'-untranslated region of PD-L1 was truncated, causing a high-level of PD-L1 protein expression. Overall, the frequent TET2 and DNMT3A mutations in EBV+ nPTCL seem to be closely associated with clonal hematopoiesis and, together with the EBV genome deletions, may contribute to the pathogenesis of this intractable lymphoma.

It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.

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.

P2, N=33, Recruiting, Great Novel Therapeutics Biotech & Medicals Corporation | Not yet recruiting --> Recruiting

P1, N=30, Active, not recruiting, Boryung Pharmaceutical Co., Ltd | Recruiting --> Active, not recruiting

P1/2, N=95, Recruiting, Zhejiang Genfleet Therapeutics Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=30, Recruiting, Bio-Path Holdings, Inc. | Trial completion date: Jan 2025 --> Jan 2026

P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P1, N=20, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=30 --> 20

P2, N=28, Recruiting, Deepa Jagadeesh | Trial completion date: Dec 2023 --> Jun 2027 | Trial primary completion date: Dec 2023 --> Jun 2024

P2, N=25, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024

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

We also perform an unsupervised clustering on the microenvironment transcriptional signatures and categorize PTCL into 4 lymphoma microenvironment subtypes based on characteristic activation of oncogenic pathways and composition of immune communities. Our findings highlight the potential clinical rationale of future precision medicine strategies that target both molecular and microenvironment alterations in PTCL.

In conclusion, 44% of ALCL patients, regardless of histological subtypes, showed a loss of/decrease in CD30 expression after receiving BV-containing therapy, but this phenomenon was not observed in CHL patients. A higher cumulative dose of BV and a lower amount of CD30 antigen in tumor cells in the initial biopsy materials might be predictors of a loss of/decrease in CD30 expression in ALCL patients.

P1, N=170, Not yet recruiting, Seagen Inc.