Neutrophil extracellular trap-related genes in PTCL: identification, prognosis and drug interaction prediction via bioinformatics-machine learning

The Role of Upfront Hematopoietic Stem Cell Transplantation (HSCT) in Peripheral T-Cell Lymphoma (PTCL) Patients in Complete Remission (CR) with a Special Focus on Nodal PTCL: Report from the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE), a Prospective Multicenter Cohort Study

A single-center retrospective study of golidocitinib for the treatment of peripheral T-cell lymphoma

A Phase II Clinical Study Exploring the Safety and Efficacy of the Oral PI3Kδ Inhibitor, Linperlisib, in Relapsed Refractory T Cell Lymphoma

A single-institution retrospective analysis of allo-HSCT for relapsed and refractory aggressive lymphomas: T-cell origin predicts better outcomes even in active disease.

A Phase II Open-Label, Multi-Center Study of Anti-CCR4 Monoclonal Antibody Mogamulizumab (KW-0761) in Patients with Previously Treated Peripheral T-Cell Lymphoma(PTCL)

Background:Peripheral T‐cell lymphomas (PTCL) are a group of rare, aggressive and diverse lymphoproliferative disorder. When patients are in the relapsed/refractory setting, the survival is mostly less than 6 months. Pralatrexate, a folate analogue metabolic inhibitor, was the first monotherapy approved to treat R/R PTCL patients. As the subtypes difference between western and eastern countries, we would like to investigate the efficacy/safety of pralatrexate in Taiwanese patients.Aims:This single‐arm, multi‐center study aims to demonstrate the efficacy/ safety of pralatrexate in R/R PTCL patients. The patients who undergo Hematopoietic Stem Cell Transplantation (HSCT) or not after pralatrexate will be also investigated individually.Methods:Eligibility criteria included age ≧ 20 with PTCL according to the NCCN diagnosis criteria, the Revised European American Lymphoma (REAL), and WHO disease classification with the following subtypes: Peripheral T‐cell lymphoma, NOS (PTCL‐NOS), Angioimmunoblastic T‐cell lymphoma (AITL), Extranodal NK/T‐cell lymphoma, nasal type (ENKL), Enteropathy‐type T‐cell lymphoma (EATL), Hepatosplenic T‐cell lymphoma (HSTCL), Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) and Adult T‐cell lymphoma/leukemia (human T‐cell leukemia virus [HTLV] 1+) (ATLL). Patients were documented disease progression after prior treatment. Intravenous pralatrexate was administrated weekly for 6 weeks in 7‐week cycles up to 5 cycles with concurrent vitamin B12 and folic acid. Patients who complete at least 1 cycle of pralatrexate and have at least 1 post‐treatment tumor assessment are defined as evaluable patients. The primary end point is Objective Response Rate (ORR, CR + PR). Secondary end points include Progression‐Free Survival (PFS), Duration of response (DoR) and Overall Survival (OS).Results:Twenty‐two patients were evaluable for efficacy per protocol definition. The subtype distribution included PTCL‐NOS (n = 9, 40.9%), AITL (n = 5, 22.7%), ENKL (n = 5, 22.7%), EATL (n = 1, 4.5%), SPTCL (n = 1, 4.5%) and ATLL (n = 1, 4.5%). The ORR was 54.5% with CR 18.2% (n = 4) and PR 36.3% (n = 8). When divided into 2 groups based on if patients received HSCT after pralatrexate, the ORR in HSCT group (n = 5) was 60% with CR 20% (n = 1) and PR 40% (n = 2), while ORR in non‐HSCT group (n = 17) was 53% with CR 18% (n = 3) and PR 35% (n = 6). At the time of data cut‐off, median PFS was 5 months (95% C.I. 5.51, 12.93), median DOR was 5.4 months (95% C.I. 2.64, 13.10) and OS not reached yet. It's notably that, among 5 patients that received HSCT successfully after pralatrexate, 4 patients are ENKL and the other is PTCL‐NOS. Except one who experienced disease progression after HSCT, the others still remain in response. It indicated that pralatrexate may play a beneficial role in bridging to transplantation in PTCL patients, especially in ENKL. Safety population analysis (n = 27) showed the most common TEAEs (grades 3–4) were: anemia (33%), stomatitis (26%), peripheral edema (22%), thrombocytopenia (15%) and leukopenia (11%).Summary/Conclusion:This interim update of this multi‐center study demonstrated the efficacy of pralatrexate monotherapy in R/R PTCL is 54.5%. Interestingly, most ENKL patients received HSCT after obtaining good disease control with pralatrexate. In addition, it showed tolerable safety profile. This is the first data demonstrated benefits of pralatrexate in R/R PTCL patients with intention or no intention to receive transplantation.image

Tucidinostat Maintenance after Achieving Objective Response to First-Line Therapy in Peripheral T-Cell Lymphoma: A Single-Center Retrospective Case-Control Study

Genetic Basis, Expression Patterns and Clinical Significance of PD-L1 in Peripheral T-Cell Lymphomas (PTCL)

Durable responses in the updated 2-year follow-up of patients from a single-center with Relapsed/Refractory peripheral T-cell lymphoma treated with golidocitinib

Galectin-1 (Gal-1) has been associated with adverse prognosis in several cancers including lymphoma entities with CD30 expression. However, Gal-1 expression has not been systematically assessed in peripheral T-cell lymphomas (PTCL). Specimens from 169 nodal PTCL were assessed for intratumoural Gal-1 expression by immunohistochemistry. Overall survival (OS) in groups exhibiting high and low Gal-1 expression was compared in the cohort and in a subset analysis of CD30-positive PTCL only. Gal-1 expression was also correlated with biomarkers of the tumour microenvironment. No significant difference in OS based on Gal-1 expression was observed in the entire PTCL cohort. However, in the CD30-positive cohort, patients with high Gal-1 levels had significantly poorer outcome (5 years OS 10%, 95% confidence interval CI, 1-36) than their low Gal-1 counterparts (5 years OS 48%, 95% CI, 30-64, P = .021). In univariate analyses age 60 or younger, non-elevated lactate dehydrogenase (LDH), and performance score less than 2 correlated with superior survival but high Gal-1 expression significantly predicted adverse outcome at both univariate (HR 2.5, 95% CI, 1.1-5.7, P = .026) and multivariate levels (HR 3.2, 95% CI, 1.2-8.5, P = .017). Tumours with high Gal-1 had few cytotoxic T cells in the tumour microenvironment. High intratumoural Gal-1 expression before therapeutic intervention correlates with adverse outcome in nodal CD30+ , ALK- PTCL patients.

Phase 2 Study of Golidocitinib, a JAK1 Selective Inhibitor, As Maintenance Therapy in Patients with Peripheral T Cell Lymphomas after First-Line Systemic Therapy (JACKPOT26)

AT56 Exerts Anti-Tumor Effects in Peripheral T Cell Lymphoma By Regulating HMOX1-Mediated Ferroptosis

Background:Peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL) are uncommon subsets of non‐Hodgkin lymphomas (NHLs), comprising less than 15% of all NHLs. The rate of refractory and relapsed (R/R) disease remains high both in PTCL and in advanced CTCL. Romidepsin is a class I selective histone deacetylase (HDAC) inhibitor approved by the FDA for R/R CTCL and PTCL patients treated with at least one prior systemic therapy. As for now, there is no real‐life data on the efficacy and safety of romidepsin in T cell lymphomas.Aims:To evaluate real‐life data concerning the efficacy and saftey of romidepsin treatment for R/R CTCL and PTCL.Methods:We conducted a multicenter retrospective study between the years 2013–2018. Demographic, clinical, laboratory and pathological data regarding PTCL and CTCL patients aged 18 years or more treated with romidepsin for R/R disease were extracted. Primary outcomes were: overall survival (OS) and event free survival (EFS). Secondary outcomes were progression free survival (PFS), response rates, duration of response (DOR) and adverse events. Efficacy outcomes were analyzed separately for PTCL and CTCL.Results:We reviewed the medical records of 53 patients with R/R PTCL (n = 42, 79.2%) or CTCL (n = 11, 20.8%) who received romidepsin between 2013 and 2018 in five medical centers nationwide. The median age was 66.2 (range 26–82) years and 64% of patients were males. The vast majority of patients had good performance status ‐ ECOG 1 or less (86%), with advanced stage (71% with stage IV disease) and multiple previous lines of treatment (median 2, range 1–5).CTCL: While the Overall response rate (ORR) was 25% and none experienced complete response (CR), the DOR was 13.8 months, (95% CI: 9.2 to 18.4) and the median OS was not reached. The median PFS and EFS were 4.7 (95% CI: 0.5–8.9) and 4.0 (95% CI: 0.4–7.5), respectively.For PTCL: The ORR was 33% (n = 13) and 12.5% (n = 5) experienced CR. The OS was 7.1 months (95% CI: 3.5 to 10.7), PFS 2.2 months (95%CI: 0.5 to 3.9) and EFS 1.9 months (95% CI: 1.2 to 2.6). In responders, the DOR was 13.4 months (95%CI: 10.0 to 16.8). In a univariate analysis for EFS, response to therapy, number of previous lines and PTCL subclass predicted for longer EFS, whereas in multivariate analysis treatment response was the only significant predictor (OR 12.67 CI 95% 3.35–47.91, p < 0.0001). In a univariate and multivariate analysis for OS, treatment response was the only predictor (figure 1; OR 4.48, CI 95% 1.57–12.79, p = 0.005).Most grade 3–4 adverse events were hematological, including neutropenia (35%), thrombocytopenia (31%) and anemia (23%). Four patients (7.7%) had febrile neutropenia and a third of all patients required hospitalization due to infection. The most common non‐hematological adverse events, except for infections, were nausea/vomiting (36%) and electrolyte disturbances (low magnesium and potassium levels in 27.5% and 19.2% of the patients, respectively).Summary/Conclusion:This real‐life experience with romidepsin confirms the results of the pivotal phase II trials. Unlike those trials, PTCL subtypes and the number of previous lines of therapy did have an impact on patient's outcomes. In addition, patients who had good response to romidepsin benefited most in terms of both EFS and OS.image

A Retrospective Study on the Efficacy and Safety of Chidamide As a Maintenance Therapy for Peripheral T-Cell Lymphoma

Hypomethylating Agent 5-Azacytidine Sensitizes Peripheral T-Cell Lymphoma to SLAMF7-Targeting Therapeutic Antibody, Elotuzumab