Treatment patterns and clinical outcomes of mantle cell lymphoma: A retrospective cohort study by CHOICE.

Regimens based on Bruton's tyrosine kinase inhibitors (BTKi) have been increasingly used to treat mantle cell lymphoma (MCL). A real-world multicenter study was conducted to characterize treatment patterns and outcomes in patients with newly diagnosed MCL by Chinese Hematologist and Oncologist Innovation Cooperation of the Excellent (CHOICE). The final analysis included 1261 patients. Immunochemotherapy was the most common first-line treatment, including R-CHOP in 34%, cytarabine-containing regimens in 21% and BR in 3% of the patients. Eleven percent (n = 145) of the patients received BTKi-based frontline therapy. Seventeen percent of the patients received maintenance rituximab. Autologous hematopoietic stem cell transplantation (AHCT) was conducted in 12% of the younger (<65 years) patients. In younger patients, propensity score matching analysis did not show significant difference in 2-year progression-free survival and 5-year overall survival rate in patients receiving standard high-dose immunochemotherapy followed by AHCT than induction therapy with BTKi-based regimens without subsequent AHCT (72% vs 70%, P = .476 and 91% vs 84%, P = .255). In older patients, BTKi combined with bendamustine plus rituximab (BR) was associated with the lowest POD24 rate (17%) compared with BR and other BTKi-containing regimens. In patients with resolved hepatitis B at the baseline, HBV reactivation rate was 2.3% vs 5.3% in those receiving anti-HBV prophylaxis vs not; BTKi treatment was not associated with higher risk of HBV reactivation. In conclusion, non-HD-AraC chemotherapy combined with BTKi may be a viable therapeutic strategy for younger patients. Anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.

Bendamustine in the treatment of patients with indolent non-Hodgkin lymphoma refractory or relapse to rituximab treatment: An open-label, single-agent, multicenter study in China.

BACKGROUND: The optimal treatment strategy for refractory or relapse (R/R) indolent non-Hodgkin lymphoma (iNHL) has not been fully identified. This study aims to investigate the efficacy and tolerance of bendamustine hydrochloride developed in native Chinese corporation in the treatment of patients with R/R iNHL. METHODS: A total of 101 patients from 19 centers were enrolled in this study from July 2016 to February 2019. Bendamustine hydrochloride (120 mg/m2 ) was given on days 1 and 2 of each 21-day treatment cycle for six planned cycles or up to eight cycles if tolerated. Parameters of efficacy and safety were analyzed. RESULTS: The median age of the patients was 53.44 (range, 24.4-74.6) years old. A total of 56 (55.44%) patients completed at least six treatment cycles, and the relative dose intensity was 93.78%. The overall response rate was 72.28%, and the median duration of response was 15.84 months (95% confidence interval [CI], 13.77-27.48 months). Median progression-free survival was 16.52 months (95% CI, 14.72-23.41 months), and the median overall survival was not reached. Grade 3 or 4 hematologic toxicities included neutropenia (77.22%), thrombocytopenia (29.70%), and anemia (15.84%). The most frequent nonhematologic adverse events (any grade) included nausea, vomiting, fatigue, fever, decreased appetite, and weight loss. Seven patients died during the trial, and four cases may be related to the investigational drug. CONCLUSIONS: This study reveals that bendamustine hydrochloride is a feasible treatment option for the indolent B-cell non-Hodgkin lymphoma patient who has not remitted or relapsed after treatment with rituximab. All adverse events were predictable and manageable.

First-line immunotherapy with anti-PD-1 antibody for extranodal NK/T-cell lymphoma: A retrospective study.

Anti-PD-1 antibody has shown certain effects in patients with newly diagnosed extranodal NK/T-cell lymphoma (ENKTL). Here, we evaluated the clinical efficacy and safety of first-line anti-PD-1 antibody for the treatment of patients with ENKTL and explored biomarkers for treatment response. The clinical data of 107 patients with newly diagnosed ENKTL were retrospectively analysed. Patients received either first-line anti-PD-1 antibody induction treatment or anti-PD-1 antibody combined with asparaginase-based chemotherapy (immunochemotherapy). We found that immunochemotherapy was an independent prognostic factor for longer PFS (p < 0.001). The overall response rate and complete remission rate of immunochemotherapy group was higher than immunotherapy induction group (86.11% vs. 62.86% and 72.22% vs. 52.29%, respectively, p = 0.013). We also observed pretreatment CD4/CD8 ratio >0.83 was significant associated with better response and longer PFS in ENKTL patients received first-line anti-PD1-antibody. Plasma copy number of EBV decreased more significantly in patients with CD4/CD8 ratio >0.83 after treatment. PD-L1 expression was associated with better response and PFS, while elevated plasma IL-6, IL-10 and IFN-γ were associated with poor prognosis. Anti-PD-1 antibody treatment showed promising results in newly diagnosed ENKTL patients. The assessment of pretreatment CD4/CD8 ratio in ENKTL seems feasible for identifying responders to anti-PD-1 antibody treatment.

A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma.

Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing nonanthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision making. Data from 722 patients with ENKTL from international centers were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n = 336) and further validated in the internal testing cohort (n = 144) and in 2 external validation cohorts (n = 142 and n = 100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the 3 validation cohorts. Patients with high- and low-risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all P < .001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. Application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significantly improved PFS and OS vs radiotherapy alone in high-risk Ann Arbor stage I patients, whereas there was no statistical difference between the 2 therapeutic modalities among low-risk patients. A nomogram was constructed comprising the classifier and clinicopathological variables; it showed remarkably better predictive accuracy than either variable alone. The 7-SNP-based classifier is a complement to existing risk-stratification systems in ENKTL, which could have significant implications for clinical decision making for patients with ENKTL.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

Review on natural killer/T-cell lymphoma.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is strongly associated with Epstein-Barr virus (EBV) and has a high prevalence in Asian and in Central and South America. About 85% of ENKTLs derive from NK cells and 15% from T-cells. Various factors have been implicated in the development of ENKTL. Molecular pathogenesis of NK/T-cell lymphomas include mutations of genes, involving in the Janus Kinase/signal transducer and activator of transcription pathway, RNA helicase family, epigenetic regulation, and tumor suppression. The relationship between ENKTL and human leukocyte antigen has been demonstrated. Radiotherapy plays a key role in the first-line treatment of early-stage. In stage III/IV diseases, non-anthracycline-regimens-containing L-asparaginase are recommended. Although clinical remission after L-asparaginase-based combination therapy has been achieved in the majority of patients with advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma-nasal type, the long-term overall survival is still poor. Recently, immunotherapy and new therapeutic targets have gained much attention. In this article, we discuss the pathogenesis, diagnosis, prognostic models and management options of ENKTL.

PD-1 blockade combined with ICE regimen in relapsed/refractory diffuse large B-cell lymphoma.

The prognosis of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. The efficacy of salvage therapy with ICE (ifosfamide, carboplatin, and etoposide) is limited. DLBCL can evade immune surveillance by upregulating programmed cell death ligand 1 (PD-L1). The purpose of this study was to explore the efficacy and safety of programmed cell death 1 (PD-1) blockade combined with ICE regimen (P-ICE) in the treatment of R/R DLBCL patients. In this study, we retrospectively explored efficacy and toxicity in R/R DLBCL patients treated with P-ICE. Prognostic biomarkers, including clinical features and molecular markers related to efficacy, were explored. From February 2019 to May 2020, a total of 67 patients treated with the P-ICE regimen were analyzed. The median follow-up time was 24.7 months (range: 1.4-39.6 months), with an objective response rate (ORR) of 62.7% and a complete response rate (CRR) of 43.3%. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 41.1% (95% CI: 35.0-47.2%) and 65.6% (95% CI: 59.5-71.7%), respectively. Age, Ann Arbor stage, international prognostic index (IPI) score, and response to first-line chemotherapy were correlated with the ORR. Grade 3 and 4 adverse events (AEs) related to the P-ICE regimen were reported in 21.5% of patients. The most common AE was thrombocytopenia (9.0%). No treatment-related deaths occurred. In patients with R/R DLBCL, the P-ICE regimen has promising efficacy and mild toxicity.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

Combination of PD-1 inhibitor with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) versus GVD regimen as second-line therapy for relapsed/refractory classical Hodgkin lymphoma.

Patients with classical Hodgkin lymphoma (cHL) who do not achieve complete remission (CR) after second-line chemotherapy have poor clinical outcomes. Besides, conventional salvage chemotherapy regimens have an unsatisfactory CR rate. The present retrospective study reports the efficacy and toxicity of the GVD (gemcitabine, vinorelbine, liposomal doxorubicin) regimen with or without programmed cell death 1 (PD-1) inhibitor for patients with cHL who failed first-line treatment. A total of 103 patients with cHL (GVD+PD-1 group, n = 27; GVD group, n = 76) with response assessment based on positron emission tomography were included. The GVD+PD-1 group tended to have a higher CR rate than GVD group (85·2% vs. 65·8%, P = 0·057) and had a better event-free survival (EFS) (P = 0·034). Subgroup analysis showed that patients with low-risk second-line International Prognostic Score might benefit from the addition of PD-1 inhibitor (GVD+PD-1 vs. GVD, 100·0% vs. 64·7%, P = 0·028) and had better EFS than GVD alone (P = 0·016). Further analysis demonstrated that PD-1 consolidation therapy might provide an EFS benefit (P = 0·007). The toxicity of the GVD+PD-1 regimen was comparable to the GVD regimen, except for higher rates of hypothyroidism and autoimmune pneumonitis, which were manageable. In conclusion, combining a PD-1 inhibitor with a GVD regimen could be a potentially effective second-line therapy for patients with cHL.

A pilot study of the use of dynamic analysis of cell-free DNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas.

The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma, is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as applying ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies. However, the genetic alterations detected in cerebrospinal fluid ctDNA only partially overlapped with those from simultaneously collected AH/VF samples, with much lower allele frequencies. Serial post-treatment AH or VF samples were available for five patients and their changes in ctDNA allele frequency displayed a similar trend as the changes in interleukin-10 levels; an indicator of response to treatment. A cohort of 23 patients with primary central nervous system lymphoma was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of primary central nervous system lymphoma than VRL patients. The objective response rate to ibrutinib treatment was much higher for patients with primary central nervous system lymphoma (64.7%, 11/17) than for those with VRL (14.3%, 1/7). In summary, we provide valuable clinical evidence that AH is a good source of tumor genomic information and can substitute VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring.

Efficacy and safety comparison between R-CHOP and modified NHL-BFM-90 regimens in children and adolescents with diffuse large B-cell lymphoma.

Studies comparing the efficacy and safety of R-CHOP and modified non-Hodgkin lymphoma Berlin-Frankfurt-Münster-90 (NHL-BFM-90) regimens in children and adolescents with diffuse large B-cell lymphoma (DLBCL) are lacking. Thus, we retrospectively analyzed 85 DLBCL patients aged ≤18 years from 2000 to 2020; 74 patients received the modified NHL-BFM-90 regimen, and 11 received the R-CHOP regimen. The 5-year OS and event-free survival (EFS) rates between the modified NHL-BFM-90 and R-CHOP regimens were 91.0% vs. 90.9% (P = 0.466) and 89.8% vs. 68.6% (P = 0.055), respectively. In the stratified analysis, the survival outcome of pediatric patients treated with the modified NHL-BFM-90 regimen was not significantly different from that of adolescent patients. The OS and EFS rates of patients with early-stage disease were both 100%. Patients in the advanced-stage group who were treated with the modified NHL-BFM-90 regimen had superior EFS rates (P < 0.05). The frequency of severe adverse events from the two regimens was similar. There were no treatment-related deaths. We concluded that the modified NHL-BFM-90 regimen has better efficacy than R-CHOP in DLBCL patients with advanced-stage disease. However, the R-CHOP regimen might be an option for early-stage DLBCL. Further prospective studies are needed to guide clinical decisions about treatment.

Optimization of high-dose methotrexate prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma: a multicenter analysis.

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare but devastating event. Intravenous high-dose methotrexate (HD-MTX) is recommended as CNS prophylaxis, but the optimal timing and dose has not been elucidated. Here, we report a multicenter analysis of prophylactic HD-MTX administration for DLBCL. Two hundred eighty-four patients receiving HD-MTX either concurrent with each induction chemotherapy cycle (n = 221) or at the end of induction therapy (EOI, n = 63) were included. Patients with CNS-IPI scoring 4-6, and/or testicular involvement, and/or double/triple hit lymphoma, were stratified into the high-risk group and the others into the moderate-risk group. Concurrent HD-MTX was associated with increased risk of grade 3/4 treatment-related toxicity (OR,1.49; P = 0.006) and subsequent chemotherapy delays (OR, 1.87; P = 0.003) in multivariate analysis. With a median follow-up of 36.0 months, no significant difference in CNS relapse rate was identified between the concurrent and EOI groups (3.2% vs 4.8%, P = 0.34), even in the high-risk group. Analysis on systemic MTX dose suggested that high-dose MTX (≥ 2 g/m2) was associated with better CNS relapse control only in the high-risk group, but not in the moderate-risk group. This study may elucidate the superiority of EOI HD-MTX to some extent. High MTX dose (≥ 2 g/m2) may not be necessary for the moderate-risk patients.

GM-CSF mediates immune evasion via upregulation of PD-L1 expression in extranodal natural killer/T cell lymphoma.

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that is used as an immunopotentiator for anti-tumor therapies in recent years. We found that some of the extranodal natural killer/T cell lymphoma (ENKTL) patients with the treatment of hGM-CSF rapidly experienced disease progression, but the underlying mechanisms remain to be elucidated. Here, we aimed to explore the mechanisms of disease progression triggered by GM-CSF in ENKTL. METHODS: The mouse models bearing EL4 cell tumors were established to investigate the effects of GM-CSF on tumor growth and T cell infiltration and function. Human ENKTL cell lines including NK-YS, SNK-6, and SNT-8 were used to explore the expression of programmed death-ligand 1 (PD-L1) induced by GM-CSF. To further study the mechanisms of disease progression of ENKTL in detail, the mutations and gene expression profile were examined by next-generation sequence (NGS) in the ENKTL patient's tumor tissue samples. RESULTS: The mouse-bearing EL4 cell tumor exhibited a faster tumor growth rate and poorer survival in the treatment with GM-CSF alone than in treatment with IgG or the combination of GM-CSF and PD-1 antibody. The PD-L1 expression at mRNA and protein levels was significantly increased in ENKTL cells treated with GM-CSF. STAT5A high-frequency mutation including p.R131G, p.D475N, p.F706fs, p.V707E, and p.S710F was found in 12 ENKTL cases with baseline tissue samples. Importantly, STAT5A-V706fs mutation tumor cells exhibited increased activation of STAT5A pathway and PD-L1 overexpression in the presence of GM-CSF. CONCLUSIONS: These findings demonstrate that GM-CSF potentially triggers the loss of tumor immune surveillance in ENKTL patients and promotes disease progression, which is associated with STAT5 mutations and JAK2 hyperphosphorylation and then upregulates the expression of PD-L1. These may provide new concepts for GM-CSF application and new strategies for the treatment of ENKTL.

A nomogram prognostic index for risk-stratification in diffuse large B-cell lymphoma in the rituximab era: a multi-institutional cohort study.

BACKGROUND: We aimed to establish a predictive prognostic risk-stratification model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: The data of 1406 primary DLBCL patients from the Sun Yat-Sen University Cancer Center were analysed to establish a nomogram prognostic index (NPI) model for predicting overall survival (OS) based on pre-treatment indicators. An independent cohort of 954 DLBCL patients from three other hospitals was used for external validation. RESULTS: Age, performance status, stage, lactate dehydrogenase, number of extranodal sites, BCL2, CD5 expression, B symptoms and absolute lymphocyte and monocyte count were the main factors of the NPI model and could stratify the patients into four distinct categories based on their predicted OS. The calibration curve demonstrated satisfactory agreement between the predicted and actual 5-year OS of the patients. The concordance index of the NPI model (0.794) was higher than the IPI (0.759) and NCCN-IPI (0.750), and similar results were obtained upon external validation. For CD5 + DLBCL patients, systemic treatment with high-dose methotrexate was associated with superior OS compared to R-CHOP-based immunochemotherapy alone. CONCLUSIONS: We established and validated an accurate prediction model, which performed better than IPI and NCCN-IPI for prognostic stratification of DLBCL patients.

Synergistic effects of α-Mangostin and sorafenib in hepatocellular carcinoma: New insights into α-mangostin cytotoxicity.

Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib. α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergistically toxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study.

This study aimed to identify the maximum-tolerated dose (MTD) of cyclophosphamide when combined with bortezomib and fludarabine (B-FC) in a phase 1b trial, and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL (rrMCL). Forty patients were enrolled between April 8, 2011, and October 10, 2015. The MTD of cyclophosphamide was identified to be 250 mg/m2 days 1-2. At a median follow-up of 31.6 months (13.5-47.4), among 32 patients in phase 2, 10 (31%) had a complete response and 13 (41%) had a partial response. The median progression-free survival was 21 months (95% CI 7.3-34.7), and the median overall survival was 32.4 months (95% CI 17.8-47.0). Grade 3-4 hematologic AEs included neutropenia (27%) and thrombocytopenia (39%). The B-FC regimen has satisfactory responses and manageable toxicities in rrMCL patients (ClinicalTrials.gov NCT01322776).

Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.

Comparison of chemotherapy with or without asparaginase for extranodal nasal NK/T-cell lymphoma in children and adolescents.

PURPOSE: As extranodal natural killer/T-cell lymphoma (ENKTL) occurs rarely in children and adolescents, standardized therapy is yet to be determined. This study aimed to describe the clinical features and determine the optimal chemotherapy regimen for childhood ENKTL. METHODS: The treatment outcomes of radiotherapy combined with asparaginase-based (P-GEMOX or P-GMED) or asparaginase-absent chemotherapy regimens (CHOP, EPOCH, or NHL-BFM-90/95) in patients aged ≤18 years with newly diagnosed ENKTL from December 2006 to December 2018 were compared. RESULTS: Among the 34 patients included in the study, 21 had stage I/II disease. The overall response rates of chemotherapy with or without asparaginase were 85.0% and 78.6%, respectively. With a median follow-up of 54 months, the 5-year event-free survival (EFS) rates of patients with stage I/II and III/IV disease were 66.2 ± 11.3% and 26.0 ± 12.8%, respectively (P = .027). In stage III/IV patients treated with asparaginase-based or asparaginase-absent regimens, the 5-year EFS rates were 40.0 ± 17.4% and 0%, respectively (P = .236). The 5-year EFS rates of stage III/IV patients who received or did not receive hematopoietic stem cell transplant were 66.7 ± 27.2% and 11.1 ± 10.5%, respectively (P = .054). In addition, chemotherapy-associated side effects were significantly less in patients treated with asparaginase-based regimens as compared to asparaginase-absent regimens in this cohort. CONCLUSION: P-GEMOX and P-GMED regimens are effective and safe for treating childhood ENKTL.

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma.

Mantle cell lymphoma is an aggressive B-cell malignancy. Current frontline chemoimmunotherapies produce high response rates but relapse is inevitable. Furthermore, the elderly and those with comorbidities are precluded from standard regimens and stem cell transplant, leaving them with limited options. Targeted therapies, including Bruton tyrosine kinase inhibitors, are an effective treatment strategy in mantle cell lymphoma. Zanubrutinib is a potent next-generation Bruton tyrosine kinase inhibitor that has demonstrated complete and sustained Bruton tyrosine kinase occupancy, minimal off-target effects and favorable pharmacokinetic/pharmacodynamic properties. Described herein is an ongoing Phase III study comparing the efficacy and safety of zanubrutinib plus rituximab followed by zanubrutinib monotherapy versus bendamustine plus rituximab followed by observation in transplant-ineligible patients with previously untreated mantle cell lymphoma. Clinical Trial Registration: NCT04002297 (ClinicalTrials.gov).

Health-related quality of life measured using EQ-5D in patients with lymphomas.

PURPOSE: This study aimed to estimate the health preference-based index scores of the population of patients with lymphoma using the EQ-5D in China. METHODS: A cross-sectional online survey was conducted to examine the health and well-being of patients with lymphoma in China. Their health-related quality of life (HRQoL; using the EQ-5D), demographic and socioeconomic characteristics, and health conditions were assessed. The data were analyzed using Pearson's χ2 test, analysis of variance, and binary logistic and Tobit regression models. RESULTS: A total of 3261 patients (sex: men = 58.5%, age: < 30 years = 9.5% and > 60 years = 24.6%) participated in the study. The mean EQ-5D-5L index and EQ-VAS scores were 0.83 and 68.8, respectively. Binary logistic regression analysis revealed that women reported more pain-related problems than men did. Unemployed participants were substantially more likely to report health problems on all the five dimensions of the EQ-5D than their employed counterparts. The Tobit regression model revealed that respondents who were older, unemployed, with low income, received chemotherapy, and with short durations reported a low index score. CONCLUSION: Using the EQ-5D, the preference-based scores of different subpopulations of patients with lymphoma may support economic evaluation by promoting the simultaneous consideration of both the reasonable use of resources and satisfactory achievement of health outcomes.