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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. 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. 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. 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. Dizal Pharmaceutical. [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma (AITL) is a unique sub-type of peripheral T-cell lymphoma (PTCL). We aimed to evaluate treatment programs and prognostic factors of 121 newly diagnosed patients with AITL in China from January 2001 to December 2018. The median age was 58 years with male predominance. Bone marrow involvement appeared in only 8.3% of patients, which was different from the previously published literature. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) were 29.7% and 44.0%, respectively. Univariate and multivariate analyses showed that involvement of >5 nodal areas, age and Beta-2 microglubulin were highly predictive of OS but only the involvement of fewer than five nodal areas was significant for PFS. We identified a novel prognostic model including the three factors that may be applied in clinical practice and offer an alternative to IPI and PIT. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation of mutation landscape with clinical outcomes in patients with peripheral T-cell lymphoma (PTCL). Methods: We retrospectively analyzed the clinicopathological and prognosis data of 53 patients with PTCL from November 2011 to December 2017. Targeted next-generation sequencing of a 659-gene panel was performed for tissues from 53 patients with PTCLs. The correlation of mutation landscape with clinical outcomes was analyzed. Results: TET2 was the most frequently mutated gene (64%), followed by RHOA (43%), PCLO (23%), DNMT3A (19%), IDH2 (17%), PIEZO1 (17%) and TP53 (15%). When mutated genes were categorized into functional groups, the most common mutations were those involved in epigenetic/chromatin modification (75%), T-cell activation (74%), and the DNA repair/TP53 pathway (64%). TET2/TP53 mutations were significantly associated with positive B symptoms (P = 0.045), and elevated lactate dehydrogenase (LDH) level (P = 0.011). Moreover, TET2/TP53 mutation was a risk factor for PTCL patient survival (HR 3.574, 95% CI 1.069 − 11.941, P = 0.039). The occurrence of JAK/STAT pathway mutations in angioimmunoblastic T-cell lymphoma (AITL) patients conferred a worse progression-free survival (HR 2.366, 95% CI 0.9130–6.129, P = 0.0334). Conclusions: Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome. [ABSTRACT FROM AUTHOR]

Background: The treatment outcomes and prognosis of lymphoma are affected by various factors such as hospital types. This study was to describe the temporal trend in the survival of lymphoma in an academic center in China. Methods: A total of 3840 consecutive patients with lymphoma diagnosed between 1996 and 2015 were reviewed. Eighty patients were excluded, and finally, 3760 patients were analyzed in this study. The cohort was divided into four groups according to calendar periods at diagnosis: 1996‐2000, 2001‐2005, 2006‐2010, and 2010‐2015. The overall survival (OS) rates among the four groups were compared. Results: The 5‐ and 10‐year OS for the whole cohort were 62% and 52%, respectively. The 5‐year OS of patient with classic Hodgkin lymphoma (cHL), mature B‐cell lymphoma (BCL), and peripheral T‐cell lymphoma (PTCL) were 79%, 63%, and 50%, respectively. Among mature BCL, the 5‐year OS was highest in follicular lymphoma (77.8%), followed by Burkitt lymphoma (76.5%), marginal zone lymphoma (74.1%), diffuse large B‐cell lymphoma (61.5%), small lymphocytic lymphoma/chronic lymphocytic leukemia (55.1%), and mantle cell lymphoma (44.3%). Among PTCL, the 5‐year OS was highest in ALK+anaplastic large cell lymphoma (79.0%), followed by ALK−anaplastic large cell lymphoma (63.1%), natural killer/T‐cell lymphoma (57.7%), angioimmunoblastic T‐cell lymphoma (34.9%, and peripheral T‐cell lymphoma not otherwise specified (27.6%). Significant improvement in the survival of lymphoma was observed, with the 5‐year OS increasing from 48% in 1996‐2000 to 65% in 2011‐2015 (P <.001). The 5‐year OS of patients with cHL, mature BCL, and PTCL changed from 55%, 49%, and 41% in 1996‐2000 to 79%, 65%, and 51% in 2011‐2015, respectively (P values were.014,.002, and.592, respectively). Conclusion: The survival of most types of lymphoma such as cHL and mature BCL, rather than PTCL, was improved significantly during the past two decades. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer (NK) cell/T‐cell lymphoma (NKTCL), a rare type of non‐Hodgkin's lymphoma, has strongly been associated with Epstein‐Barr virus (EBV) infection. However, there are no EBV genomes isolated from NKTCL, and the roles the variations of EBV strains play in the pathogenesis of NKTCL are still unclear. Materials and Methods: In this study, whole EBV genomes from eight primary NKTCL biopsy specimens were obtained using next‐generation sequencing, designated NKTCL‐EBV1 to NKTCL‐EBV8. Results: Compared with the six mostly referenced EBV strains, NKTCL‐EBVs closely resemble the GD1 strain but still harbor 2,072 variations, including 1,938 substitutions, 58 insertions, and 76 deletions. The majority of nonsynonymous mutations were located in latent and tegument genes. Moreover, the results from phylogenetic analysis of whole NKTCL genomes and specific genes demonstrated that all the NKTCL‐EBVs were related to Asian EBV strains. Based on the amino acid changes in certain residues of latent membrane protein 1 (LMP1) and EBV‐determined nuclear antigen 1 (EBNA1), all the NKTCL‐EBVs were sorted to China 1 and V‐val subtype, respectively. Furthermore, changes in CD4+ and CD8+ T‐cell epitopes of EBNA1 and LMP1 may affect the efficacy for a cytotoxic T lymphocyte (CTL)‐based therapy. Conclusion: This is the first large study to our knowledge to obtain EBV genomes isolated from NKTCL and show the diversity of EBV genomes in a whole genome level by phylogenetic analysis. Implications for Practice: In this study, the full‐length sequence of Epstein‐Barr virus (EBV) isolated from eight patients with nasal natural killer/T‐cell lymphoma (NKTCL) was determined and further compared with the sequences previously reported isolated from other malignancies. Phylogenetic analysis showed that NKTCL‐EBV strains are close to other Asian subtypes instead of non‐Asian ones, leading to the conclusion that EBV infections are more likely affected by different geographic regions rather than particular EBV‐associated malignancies. Therefore, these data have implications for the development of effective prophylactic and therapeutic vaccine approaches targeting the personalized or geographic‐specific EBV antigens in these aggressive diseases. Extranodal natural killer cell/T cell lymphoma (NKTCL) has been associated with Epstein‐Barr virus (EBV) infection. This article describes the distribution of genetic variation in EBV genomes isolated from NKTCL biopsy samples and evaluates genomic diversity in the EBV strains. [ABSTRACT FROM AUTHOR]

Purpose: The standard treatment for peripheral T-cell lymphomas (PTCLs) is undetermined. We designed a CHOPE/G regimen (cyclophosphamide, pirarubicin, vincristine, prednisolone, and etoposide alternating with a gemcitabine-based regimen) as the first-line treatment of PTCLs and compared with CHOP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) and CHOPE (CHOP plus etoposide) regimen to evaluate the optimal chemotherapy regimen.Methods: 116 previously untreated PTCL patients received CHOP (N = 46), CHOPE (N = 46), or CHOPE/G (N = 24) regimen at Peking University Cancer Hospital from 2009 to 2017 and were retrospectively analyzed.Results: The overall response rates (ORRs) of the CHOP, CHOPE, and CHOPE/G groups were 82.6%, 76.1%, and 75.0% (p = 0.673), with complete response (CR) rates of 32.6%, 56.5%, and 45.7% (p = 0.063), respectively. Within a median follow-up time of 35.5 months, the 3-year overall survival (OS) rates of the CHOP, CHOPE, and CHOPE/G groups were 37.0%, 47.0%, and 56.3% (p = 0.107), and the 3-year progression-free survival (PFS) rates were 19.9%, 29.9%, and 5.3% (p = 0.093), respectively. Compared with the CHOP regimen alone, CHOPE had a significantly higher CR rate (p = 0.021) with more favorable OS (p = 0.046). The CHOPE/G regimen did not improve the ORR, CR rate, or OS compared with either the CHOP or CHOPE, with a significantly poorer PFS compared with the CHOPE regimen (p = 0.029). Anemia and thrombocytopenia occurred most frequently in the CHOPE/G group (anemia 83.3%, p = 0.035; thrombocytopenia 50%, p = 0.015).Conclusions: Compared with CHOP alone, CHOPE regimen improved the efficacy and survival; while the addition of gemcitabine in the front-line therapy resulted in more adverse events without benefit of survival. [ABSTRACT FROM AUTHOR]

Background: The combination of chemotherapy and L-asparaginase (L-ASP) treatment significantly increased survival rate in an adult patient with extranodal natural killer (NK)/T-cell lymphoma (NKTCL). However, hypersensitivity reactions of L-ASP in some patients limited its application. Polyethylene glycol-conjugated asparaginase (PEG-ASP) has a lower immunogenicity and longer circulating half-life than unconjugated L-ASP, and has been reported to be effective and well-tolerated in children with acute lymphoblastic leukemia. Cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisolone (CHOP) is the most common chemotherapy for non-Hodgkin lymphoma. In this report, we sought to study the efficacy and safety of PEG-L- CHOP in NKTCL in adult Chinese patients.Methods: Our study is a prospective, multi-center, open-label clinical trial. Patients with newly diagnosed adult NKTCL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included six cycles of PEG-L-CHOP regimen. Radiotherapy was scheduled after 2-4 cycles of PEG-L-CHOP regimen, depending on the stage and primary anatomic site.Results: We enrolled a total of 33 eligible patients. All 33 patients completed 170 cycles of chemotherapy combined with radical radiotherapy. The overall response rate was 96.9% (32/33) with 75.8% (25/33) achieving complete responses and 21.2% (7/33) achieving partial responses. The overall survival (OS) at 1, 2, 3-year were 100, 90.61 and 80.54%, respectively. The major adverse effects were bone marrow suppression, reduction of fibrinogen level, liver dysfunction, and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions: PEG-L-CHOP chemotherapy in combination radiotherapy is safe and durably effective treatment for adult extranodal NK/T-cell lymphoma with fewer allergic reactions. This study was approved by the Peking University Beijing Cancer Hospital Ethics Review Committee (reference number: 2011101104). The clinical trial registration number ChiCTR1800016940 was registered on July 07, 2018 at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ). The clinical trial was registered retrospectively. [ABSTRACT FROM AUTHOR]

In order to investigate whether the SUVmax-liver-based interpretation could improve prognostic accuracy of interim (PET-4) and posttreatment PET/CT (PET-end), 115 patients with newly diagnosed DLBCL were recruited in the study. ROC analysis revealed the optimal threshold is 1.6-fold of SUVmax-liver for PET-4 and 1.4-fold of SUVmax-liver for PET-end. The SUVmax-liver-based interpretation had a perfect interobserver agreement, higher prognostic accuracy and positive predictive value than 5-point scale and %DSUVmax criteria in both PET-4 and PET-end. Dramatic differences in the outcome between patients with positive and negative PET-4/PET-end were demonstrated using Kaplan-Meier survival curves (p<.05). Univariate and multifactor analysis found PET-4 and PET-end were independent prognostic factors for the outcome of DLBCL. In conclusion, the SUVmax-liver-based interpretation were superior to 5-point scale and %ΔSUVmax criteria in analyzing the PET-4 and PET-end for the prognosis of DLBCL patients. [ABSTRACT FROM AUTHOR]

Extranodal natural killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (HPS) (NK/T-LAHS) is a heterogeneous and life-threatening disease, which warrants investigation of its risk factors and clinical features. We retrospectively analyzed the clinical records of 202 patients with extranodal NK/T cell lymphoma and compared the characteristics and survival of extranodal NK/T cell lymphoma patients with and without HPS. The cumulative incidence of NK/T-LAHS was 11.4 % (23/202). In a multivariate logistic regression model, younger age (p = 0.012), bone marrow involvement (p = 0.012), and reduced serum albumin (p < 0.001) were independent risk factors for developing HPS in patients with extranodal NK/T cell lymphoma. The survival of extranodal NK/T cell lymphoma patients was aggravated when complicated with HPS, with an overall 2-year survival of 72.1 and 30.4 %, respectively (p < 0.001). Six patients with HPS onset at lymphoma diagnosis tended to have a poor performance status (p = 0.040), while the rate of elevated bilirubin was significantly higher in 17 patients with HPS onset at lymphoma relapse (p = 0.045). After HPS onset, treatment response was poor (response rate, 17.4 %) and survival was dismal with a median of 26 days. Univariate analysis showed that patients with lactate dehydrogenase >1000 U/L (p = 0.048) and disseminated intravascular coagulation (p = 0.004) had shorter survival time. Extranodal NK/T cell lymphoma was frequently complicated with HPS, and survival was discouraging in this circumstance. Intensive chemotherapy regimens including L-asparaginase or pegaspargase and allogeneic stem cell transplantation should be investigated. [ABSTRACT FROM AUTHOR]