Brentuximab Vedotin Retreatment in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma or Peripheral T-Cell Lymphoma: A Retrospective United States Claims Analysis.

Brentuximab vedotin (BV) monotherapy (BV-M) and combination (BV-C) therapies are safe and effective for classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphomas (PTCLs). Although the sample sizes have been small (12-29 patients), in clinical studies, response rates of 53-88% have been reported for BV retreatment in patients with an initial BV response. We evaluated the real-world characteristics and treatment patterns of cHL/PTCL patients who received BV and were retreated in the United States. Symphony Health Patient Claims (11/2013-1/2022) were retrospectively analyzed to identify cHL/PTCL patients treated with BV and retreated with BV-M, BV-C, or non-BV therapy. Patient characteristics were described by retreatment, and predictors of BV-M retreatment were identified. Among the cHL and PTCL patients treated with BV (n = 6442 and 2472, respectively), 13% and 12%, respectively, were retreated with BV; the median times from initial BV to BV-M retreatment were 5 and 7 months, respectively; and the numbers of BV-M retreatment doses were 4 and 5, respectively. Among cHL patients, the predictors of BV-M retreatment were age (18-39 vs. ≥60 years), sex (women vs. men), and previous stem cell transplantation (yes vs. no). Among PTCL patients, the only predictor of BV-M retreatment was systemic anaplastic large-cell lymphoma subtype (yes vs. no). Real-world data support clinical study results suggesting earlier BV treatment be considered, as BV retreatment may be an option.

Clinicopathologic analysis of nodal T-follicular helper cell lymphomas, a multicenter retrospective study from China.

Background: Nodal T-follicular helper cell lymphomas (nTFHLs) represent a new family of peripheral T-cell lymphomas (PTCLs), and comparative studies of their constituents are rare. Methods: This study retrospectively enrolled 10 patients with nTFHL-F and 30 patients with nTFHL-NOS diagnosed between December 2017 and October 2023 at six large comprehensive tertiary hospitals; 188 patients with nTFHL-AI were diagnosed during the same period at the First Affiliated Hospital of Zhengzhou University for comparison. Results: Compared with nTFHL-AI, nTFHL-NOS patients exhibited better clinical manifestations, lower TFH expression levels, and a lower Ki-67 index. However, no differences in clinicopathological features were observed between nTFHL-F and nTFHL-AI patients as well as nTFHL-NOS patients. According to the survival analysis, the median OS for patients with nTFHL-NOS, nTFHL-AI, and nTFHL-F were 14.2 months, 10 months, and 5 months, respectively, whereas the median TTP were 14 months, 5 months, and 3 months, respectively. Statistical analysis revealed differences in TTP among the three subtypes(P=0.0173). Among the population of patients receiving CHOP-like induction therapy, there were significant differences in the OS and TTP among the nTFHL-NOS, nTFHL-AI, and nTFHL-F patients (P=0.0134, P=0.0205). Both the GDPT and C-PET regimens significantly improved the ORR, OS, and PFS in nTFHL patients. Conclusion: There are significant differences in the clinical manifestations, pathology, and survival outcomes among the three subtypes of nTFHLs. However, further research with a larger sample size, and involving clinical pathology and molecular genetics is needed to determine the distinctive biological characteristics of these tumors.

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma.

PURPOSE: To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL). METHODS: Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed. RESULTS: Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017-24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOAG17V (P = 0.023), and TET2 mutations (P = 0.032). CONCLUSION: 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.

The RNA sequencing results revealed the expression of different genes and signaling pathways during chemotherapy resistance in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin's lymphoma that occurs primarily at extranodal sites and is commonly treated using chemotherapy and radiotherapy. PTCL is more malignant than other lymphoid tumors, resulting in a poor prognosis.The 5-year recurrence rate remains high, and there is a lack of standard treatment for patients with relapse-resistant disease. However, the molecular mechanisms underlying the resistance of peripheral T-cell lymphoma cells to chemotherapeutic drugs, as well as identifying strategies to overcome drug resistance remains unclear. In this study, we aimed to identify pivotal genes and signaling pathways associated with chemotherapy resistance in PTCL. METHODS: In this study, a total of 5 healthy controls and 7 clinical patients were enrolled; 4 patients were classified as chemotherapy sensitive, and 3 patients were classified as chemotherapy resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells. RNA sequencing was conducted on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, the expression patterns of the DEGs associated with the most enriched signaling pathways, with a special focus on cancer-related genes, were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral TCL patients. RESULTS: RNA sequencing (RNA-seq) analysis revealed 4063 differentially expressed genes (DEGs) in peripheral T-cell lymphoma specimens from patients with chemotherapy resistance, of which 1128 were upregulated and 2935 were downregulated. Subsequent quantitative gene expression analysis confirmed a differential expression pattern in all the libraries, with 9 downregulated genes and 10 upregulated genes validated through quantitative real-time PCR in 6 clinical specimens from patients with chemotherapy resistance. KEGG pathway analysis revealed significant alterations in several pathways, with 6 downregulated pathways and 9 upregulated pathways enriched in the DEGs. Notably, the TNF signaling pathway, which is extensively regulated, was among the pathways that exhibited significant changes. These findings suggest that DEGs and the TNF signaling pathway may play crucial roles in chemotherapy resistance in peripheral T-cell lymphoma. CONCLUSION: 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.

Extranodal natural killer/T-cell lymphoma coexisting with peripheral T-cell lymphoma, not otherwise specified.

We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. 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.

18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

A case of peripheral T-cell lymphoma in which therapy-related myelodysplastic syndrome developed and a second autologous transplantation was performed.

We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.

Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).

NOT OTHERWISE SPECIFIED T-CELL LYMPHOMA: OUTCOMES OF A SINGLE CENTER STUDY.

BACKGROUND: The peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common subtype of peripheral T-cell lymphoma (PTCL). It constitutes approximately 25% of all PTCLs and accounts for more than 15% of all lymphomas. The results of the first Ukrainian prospective study of patients with PTCL-NOS are presented in the article. The aim of the study was to analyze the morbidity of PTCL patients and the treatment performed, to evaluate overall survival and progression-free survival, and to determine the factors that predict the treatment response. PATIENTS AND METHODS: An analysis was performed on the data of 31 patients diagnosed with peripheral PTCL-NOS from February 2018 to the present. T-cell lymphoid neoplasms were diagnosed according to the 2016 WHO classification. The treatment regimens were in alignment with ESMO and NCCN guidelines. More than 90% of patients were prescribed anthracycline-based regimens (CHOP; CHOEP - cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone). An initial treatment was performed with CHOP-based regimens in 38.70% (n = 12) of patients, with the addition of etoposide in 58.06% of patients (n = 18). RESULTS: The response was assessed according to the response criteria for malignant lymphoma (Cheson, 2008, 2014). The overall response to therapy was 58.06% (n = 18), with complete responses in 29.03% of patients and partial responses in 29.03% of patients. The stabilization of the disease occurred in 3.44%, while the disease progression in 41.37% of patients. The 12-month and 24-month survival rates were 75.44% and 50.81%, respectively. The 12-month and 24-month progression-free survivals were 47.68% and 33.1%, respectively. Ki-67 overexpression (> 65%) was a negative prognostic factor. CONCLUSIONS: The results of the treatment of PTCL obtained in a Ukrainian population study are similar to those in other European studies, all of which remain unsatisfactory. Further research is required to develop a new strategy for examination and therapy to improve treatment outcomes. The emphasis should be placed on the pragmatic clinical trials comparing the efficacy of first-line treatment in PTCL patients with both favorable and unfavorable clinical factors.

Aggressive T-cell lymphomas: 2024: Updates on diagnosis, risk stratification, and management.

INTRODUCTION: Aggressive T-cell lymphomas continue to have a poor prognosis. There are over 30 different subtypes of peripheral T-cell lymphoma (PTCL), and we are now beginning to understand the differences between the various subtypes beyond histologic variations. MOLECULAR PATHOGENESIS OF VARIOUS SUBTYPES OF PTCL: Gene expression profiling and other molecular techniques have enabled deeper understanding of differences in various subtypes as reflected in the latest 5th WHO classification of PTCL. It is becoming increasingly clear that therapeutic approaches that target specific cellular pathways are needed to improve the clinical outcomes of PTCL. TARGETED THERAPIES: There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. This includes the CD30 directed antibody drug conjugate brentuximab vedotin. Other notable targets are phosphatidylinositol 3-kinase inhibitors, histone deacetylase inhibitors, CD25, and chemokine receptor 4. Anaplastic lymphoma kinase (ALK) inhibitors are promising for ALK expressing tumors. IMMUNOTHERAPIES: Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL. The use of checkpoint inhibitors in the treatment of PTCL is still controversial, with best results seen in cases of extranodal natural killer cell/T-cell lymphoma. Bispecific antibody-based treatments and chimeric antigen receptor cell-based therapies are in clinical trials.

Prognostic Significance Of Sequential 18f-fdg Pet/Ct During Frontline Treatment Of Peripheral T Cell Lymphomas.

BACKGROUND/AIMS: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. METHODS: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. RESULTS: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2-3, and 4-5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). CONCLUSION: The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.

Clinicopathological comparison between PTCL-TBX21 and PTCL-GATA3 in Japanese patients.

AIM: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a heterogeneous disease that can be classified into the PTCL-TBX21 and PTCL-GATA3 subtypes. METHODS: In this study, we compared the clinicopathological features of PTCL-NOS in a Japanese cohort, classified using an IHC algorithm. RESULTS: One hundred patients with PTCL-NOS were categorized as having PTCL-TBX21 (n = 55), PTCL-GATA3 (n = 24), or PTCL-unclassified (n = 21). When comparing PTCL-TBX21 and PTCL-GATA3, PTCL-TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity-related genes, such as PD-L1, LAG3, and IDO1, in PTCL-TBX21 than in PTCL-GATA3. PTCL-GATA3 had significantly worse overall survival (OS) than those with PTCL-TBX21 (p = 0.047), although a similar tendency was observed for progression-free survival (PFS) (p = 0.064). PTCL-GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09-3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93-4.61; p = 0.074). In the PFS analysis, PTCL-GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08-3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07-5.11; p = 0.032). CONCLUSION: The classification of PTCL-NOS into PTCL-TBX21 and PTCL-GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice.

Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study.

PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.

Therapeutic challenges in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.

The prognostic significance of POD24 in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. METHODS: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. RESULTS: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, ß2-microglobulin (ß2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. CONCLUSION: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study.

BACKGROUND: Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. METHODS: We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04105010, and is closed to accrual and follow-up is ongoing. FINDINGS: Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51-67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9-18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7-55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3-4 drug-related treatment-emergent adverse events. The most common grade 3-4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. INTERPRETATION: In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. FUNDING: Dizal Pharmaceutical.

SOHO State-of-the-Art Updates and Next Questions: Treatment for Newly Diagnosed Peripheral T-Cell Lymphomas.

Although a rare subset of non-Hodgkin lymphomas, peripheral T-cell lymphomas (PTCL) account for a disproportionate proportion of patient mortality. Conventional therapies are derived from experience treating aggressive B-cell lymphomas and center around CHOP-based chemotherapy. However, due to the unique biology and diverse subtypes of PTCL, most patients fail to durably respond to this approach and 5-year survival is only 20% to 30%. There have been multiple attempts to improve outcomes for patients with PTCL. Among the more successful strategies are the use of consolidative autologous stem cell transplant, the augmentation of CHOP with etoposide (CHOEP), and the use of brentuximab vedotin in CD30-positive PTCL. Advances in the understanding of histology-specific biology has cultivated enthusiasm to evaluate hypomethylating agents, histone deacetylate inhibitors, and phosphoinositol-3-kinase inhibitors in the frontline setting. Improvements in monitoring disease response and prognostication including the use of cell-free DNA, mutational profiling, and interim PET/CT imaging are also on the horizon. For patients with acute T-cell leukemia/lymphoma, the use of mogamulizumab-based therapy in the frontline setting may lead to advances in care. The true impact of these new-era therapies will only be elucidated as clinical practices incorporate the rapidly changing evidence.

Real-world treatment patterns, healthcare resource utilization and costs among patients with peripheral T-cell lymphoma.

Objective: To evaluate treatment patterns, healthcare resource utilization (HRU) and costs among peripheral T-cell lymphoma (PTCL) patients in the USA. Methods: A retrospective cohort study, using the IQVIA PharMetrics® Plus claims database from 1 April 2011 to 30 November 2021, identified PTCL patients receiving systemic treatments. Three mutually exclusive subcohorts were created based on line of therapy (LOT): 1LOT, 2LOT and ≥3LOT. Common treatment regimens, median time on treatment, all-cause and PTCL-related HRU and costs were estimated. Results: Among 189 PTCL patients identified, 61.9% had 1LOT, 21.7% had 2LOT and 16.4% had ≥3LOT. The most common treatment regimens in the 1LOT were CHOP/CHOP-like, CHOEP/CHOEP-like and brentuximab vedotin; monotherapies were most common in the 2LOT and ≥3LOT. All-cause and PTCL-related hospitalizations and prescriptions PPPM increased with increasing LOT. Nearly 70% of total treatment costs were PTCL related. Conclusion: Higher utilization of combination therapies in the 1LOT and monotherapies in subsequent LOTs were observed, alongside high PTCL-related costs.

Peripheral T-cell lymphomas (PTCL) are a rare and fast-growing form of blood cancer. About 8000­12,000 people in the USA are diagnosed with PTCL every year. As it is a rare disease and has many types, and there is a limited understanding of the patients who have PTCL and the treatments they receive in the real world. The purpose of this study was to evaluate how these patients are treated, what are they treated with and what are the costs of these treatments in the USA. The data collected on these patients was divided into three groups based upon the number of lines of treatment/therapy (LOT) they received: 1LOT, 2LOT and ≥3LOT. This study researched different treatments and their duration in each line of therapy. Among 189 PTCL patients included in the study, the average age of patients was 55 years and 62% were male. Among these patients, 62% had 1LOT, 22% had 2LOT and 16% had ≥3LOT. The most common treatments in the 1LOT were traditional chemotherapy regimens followed by targeted therapies: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-like, CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone) or CHOEP-like, and brentuximab vedotin. Treatment regimens with only one drug were most common in the 2LOT and ≥3LOT. The total cost of PTCL treatment in the USA is very high; 70% of this cost is related to their treatment with various drugs. More research is needed to better understand the treatment and cost of this rare cancer.