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AbstractThis is a retrospective study conducted to determine whether there is an optimal regimen for elderly diffuse large B-cell lymphoma (DLBCL) patients. We selected patients aged 80 years or older who received the frontline chemoimmunotherapy of standard-dose rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), reduced dose of R-CHOP (R-miniCHOP), or rituximab and bendamustine (BR). Patients with standard dose of R-CHOP presented a better overall response rate than those with R-miniCHOP (p = 0.047). However, there was no significant difference in progression-free survival (PFS) or overall survival (OS) among the groups. Eastern Cooperative Oncology Group performance status of 0 or 1, serum albumin ≥3.5 g/dL, early stage, and GCB subtype were the factors associated with superior PFS and OS. In conclusion, no single regimen was found to be superior for elderly DLBCL patients. Rather than selecting regimen depending on sole age, comprehensive evaluation should be done before chemotherapy initiation. [ABSTRACT FROM AUTHOR]

AbstractT-cell/histiocyte-rich B-cell lymphoma (THRLBCL) is an uncommon variant of diffuse large B‐cell lymphoma (DLBCL). Historically, it is considered an aggressive variant with poorer outcomes; however, recent analyses suggest that outcomes may be better for patients treated in the rituximab era. We reviewed THRLBCL cases who were diagnosed in MSKCC from January 2000 to October 2019. A total of 67 patients were included with a median follow-up of 5.4 years (0.5–13.8). Frontline treatment included R-CHOP or R-CHOP-based treatment in 48%, R-EPOCH in 12%, R-CHOP/R-ICE in 33% and other palliative treatments in 7.5%. In the whole cohort, 5-year EFS and OS was 59% and 79%, respectively. In an analysis of patients who received therapy with R-CHOP-14 × 4 followed by ICE/R-ICE × 3 compared to patients who were treated with R-CHOP or R-CHOP based treatment, CR rates were 95% and 70%, respectively (p = 0.023). The R-CHOP/R-ICE regimen was also associated with higher event-free survival (5-year EFS of 80% vs 50%; p = 0.006) and overall survival (5-year OS of 100% vs 72%; p = 0013). Our study demonstrates better outcomes among patients with THRLBCL compared to historical data. Our findings suggest that treatment with a higher intensity regimen with noncross resistance, such as R-CHOP/R-ICE is reasonable approach for patients with newly diagnosed THRLBCL. [ABSTRACT FROM AUTHOR]

AbstractTreatment strategies for early stage diffuse large B-cell lymphoma (ES-DLBCL) include R-CHOP, with a similar schedule to that used in advanced stage, or a reduced number of cycles followed by radiation therapy (RT). We retrospectively analyzed 179 ES-DLBCL patients, managed according to the clinical practice. Treatment regimens include chemoimmunotherapy 4–6 cycles +/- RT as consolidation. First-line therapy was R-CHOP/CHOP-like in 88.8% of cases. RT as consolidation was administered to 29.9% of cases. Complete response rate was 87.2%, median PFS and OS were not reached. IPI 2–3 and first-line regimen with 3–4 cycles of R-CHOP without RT were the 2 prognostic variables for OS in multivariate analysis. After a median follow-up of 48 months, 31 patients died (17.3%). We suggest that both R-CHOP 6 cycles and 3–4 cycles followed by RT as consolidation seem to be valid first-line regimens, while an abbreviated strategy without RT could be associated to inferior outcome. [ABSTRACT FROM AUTHOR]

AbstractPatients with relapsed/refractory primary central nervous system lymphoma (R/R PCNSL) usually have a poor prognosis and limited treatment options. We respectively reviewed 38 patients with R/R PCNSL treated with zanubrutinib-based regimens in our center. The overall response rate, complete response rate and disease control rate were 76.3%, 47.4% and 92.1%, respectively. The median progression-free survival (PFS) was 31.0 months, the median overall survival (OS) was not reached. Unitivariate analysis by Cox’s proportional hazards model revealed that overall response (vs. no response, HR = 0.18, 95%CI:0.07,0.48, p = 0.001), long duration of zanubrutinib (≥6months vs 2-5 months, HR = 0.20, 95%CI:0.06,0.63, p = 0.006) were independent factors for prolonged PFS. The log-rank analysis indicated a prolongation of PFS among patients exhibiting a higher Tumor mutational burden (TMB, ≥14.75muts/Mb) following zanubrutinib-based treatment (p = 0.016). Our data showed promising efficacy with tolerable safety of zanubrutinib-based therapies in patients with R/R PCNSL. Long duration of zanubrutinib may be associated with prolonged PFS. [ABSTRACT FROM AUTHOR]

AbstractThe cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations. This study introduces gneSeqCOO, an algorithm using bulk RNA Sequencing (RNASeq) profiles of individual tumor biopsies for COO classification based on a fixed reference. This method produced consistent per-sample results and was robust to variation in RNA quality and sequencing bias. Validation in >1000 DLBCL samples showed high concordance with the NanoString LST assay, even in cohorts containing only one COO subtype. gneSeqCOO presents a robust and versatile alternative to existing assays, potentially reducing the need for additional samples where RNASeq was already generated. The package is available at https://github.com/Genentech/gneSeqCOO. [ABSTRACT FROM AUTHOR]

Double-hit lymphoma (DHL) is a high-risk subtype of large B-cell lymphoma, defined by concurrent rearrangements MYC and BCL2. The diagnosis is confirmed through histologic and immunophenotypic examination and fluorescence in situ hybridization (FISH) to demonstrate the rearrangements. DHL morphology ranges from DLBCL to high-grade B-cell lymphoma which can resemble Burkitt lymphoma and is almost always germinal center B-cell like (GCB). Prognosis is influenced by elevated lactate dehydrogenase (LDH), advanced stage, and extranodal involvement, among other factors. Treatment outcomes vary, but intensive chemotherapy regimens such as dose-adjusted EPOCH-R have shown the most promising results, though low-risk cases do occur and may do well with less intensive treatments. Recent therapeutic advances such as CAR-T cells and bispecific antibodies offer promise for patients with relapsed/refractory disease. This review synthesizes data from recent literature to provide a comprehensive analysis of the molecular underpinnings, diagnostic criteria, prognostic factors, and therapeutic strategies for DHL. [ABSTRACT FROM AUTHOR]

Richter's transformation (RT) is defined as the evolution of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This complication is rare and aggressive, with poor prognosis and dismal survival. Clonal relationship with the underlying CLL/SLL, observed in ∼80% of cases, represents one of the main factors affecting prognosis. Treatment has been historically based on chemoimmunotherapy, but frequent mutations in genes involved in cell survival and proliferation—such as TP53, NOTCH1, MYC, CDKN2A—confer resistance to standard treatments. During the last years, advances in the knowledge of the biological mechanisms underlying RT allowed to identify genetic and molecular lesions that can potentially be targeted by novel selective agents. Pathway and checkpoint inhibitors, bispecific antibodies and CAR T-cell therapy are currently under investigation and represent promising treatment options. This review summarizes current biological evidence and available data on novel therapeutic agents. [ABSTRACT FROM AUTHOR]

The ideal treatment paradigm for bulky diffuse large B-cell lymphoma (DLBCL) remains uncertain. We investigated the impact of tumor bulk in patients treated with systemic therapy alone through Alliance/CALGB 50303. Data from this trial were obtained from the National Cancer Institute's NCTN/NCORP Data Archive. The study assessed the size of nodal sites and estimated progression-free survival (PFS) using Cox proportional hazards models. Stratified analysis factored in International Prognostic Index (IPI) risk scores. Out of 524 patients, 155 had pretreatment scans. Using a 7.5 cm cutoff, 44% were classified as bulky. Bulk did not significantly impact progression-free survival (PFS), whether measured continuously or at thresholds of >5 or >7.5 cm (p = 0.10–p = 0.99). Stratified analyses by treatment group and IPI risk group were also non-significant. In this secondary analysis, a significant association between bulk and PFS was not identified. KEY POINTS: The prognosis of upfront tumor bulk in DLBCL remains unclear. In this secondary analysis of a phase III trial comparing DA-EPOCH-R to R-CHOP, a significant association between upfront tumor bulk and PFS was not identified. [ABSTRACT FROM AUTHOR]

Up to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria. [ABSTRACT FROM AUTHOR]

AbstractChimeric antigen receptor (CAR) T-cell therapy has changed treatment landscape of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and more older patients have been treated with curative intent for R/R disease, including patients previously deemed unfit for autologous stem-cell transplant with a broader application of CAR T-cell therapy. Due to the unique CAR T-cell-related toxicity and special attention needed in treating older patients, optimal patient selection and management of CAR T-cell therapy in older patients are becoming more critical. More data are emerging in the field; multiple approaches, such as geriatric and frailty assessment and multi-disciplinary work with geriatrics, are being studied for CAR T-cell therapy application. Studies support the safe use of CAR T-cell therapy in older patients, however, application of geriatric assessment tools and maximizing multi-disciplinary approach to tailor supportive care are critical to reduce morbidity and improve outcomes in older patients. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that a low skeletal muscle mass (SMM) is an adverse factor for overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). However, its association with the treatment response has not been extensively investigated. This study aimed to determine the association between low skeletal muscle mass (SMM) and treatment response in DLBCL patients. We conducted a retrospective cohort study of 123 patients with DLBCL, in whom SMM was assessed using computed tomography before chemotherapy administration. The demographic characteristics of the patients with low SMM and those with normal SMM were not statistically different. However, there were notable differences in weight and BMI; patients with low SMM had a lower mean weight (59.2 vs 63, p = 0.002) and a higher proportion of patients with normal BMI (61.5% vs. 21.1%, p < 0.001). In addition, patients with low SMM were more likely to receive R-CHOP-like treatment (21.2% vs. 7%, p = 0.022) and experienced more delays in administration (42.9% vs. 33.3%, p = 0.452). Low SMM was not associated with failure to achieve CR (HR 1.9; 95% CI [0.9–4.1] p = 0.84), but it was reported to risk OS in univariate analysis (HR 2.1; 95% CI [1.03–4.2], p = 0.041). An interesting result was the interaction of low SMM with hypertension as a risk factor for not achieving CR (HR 2.7; 95% CI [1.1–6.5] p = 0.034) or OS (HR 7.9; 95% CI [3.4–18.8] p < 0.001). Low SMM was not a risk factor for achieving CR in patients with DLBCL and seemed to play a role in OS. [ABSTRACT FROM AUTHOR]

This study used COTA de-identified data (2010–2021) of patients in the US to explore outcomes of novel therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in real-world settings. Demographics, clinical characteristics, and clinical outcomes of patients with R/R DLBCL who received novel treatments including chimeric antigen receptor T-cell (CAR T) therapy and tafasitamab- or polatuzumab-based therapies were evaluated. Overall, 175 patients with R/R DLBCL were analyzed; 73, 69, and 27 received CAR T therapy, polatuzumab-based regimens, and tafasitamab-based regimens, respectively. In patients who had ≥1 prior lines of therapy (i.e. starting second-line or later therapy; 2 L+), CAR T, polatuzumab-based regimens, and tafasitamab-based regimens achieved a median overall survival of 26.5, 7.8, and 6.3 months, respectively. Outcomes were particularly poor for patients with relapse following CAR T, indicating that polatuzumab- and tafasitamab-based regimens in 2 L + R/R DLBCL have suboptimal outcomes in the real world. Additional treatment options are needed. [ABSTRACT FROM AUTHOR]

We aim to investigate cardiovascular mortality risk among diffuse large B-cell lymphoma (DLBCL) patients and explore cardiovascular mortality trends in the past decades in United States. We extracted data from the Surveillance, Epidemiology, and End Results database for adult patients diagnosed with DLBCL between 1975 and 2019. Standardized mortality ratio, joinpoint regression analysis, and competing risk model were analyzed. Overall, 49,918 patients were enrolled, of whom 4167 (8.3%) cardiovascular deaths were observed, which was 1.22 times the number expected (95%CI, 1.19–1.26). During 1985–2019, the incidence-based cardiovascular mortality rate increased by 0.98% per year (95%CI, 0.58–1.39%), with statistically significant increases in age groups younger than 75 years. The cumulative mortality from cardiovascular disease increased by age but never exceeded that from DLBCL. Older age, male sex, earlier year of diagnosis, lower tumor stage at diagnosis, chemotherapy, radiotherapy, and surgery were all poor prognostic factors for cardiovascular mortality. [ABSTRACT FROM AUTHOR]

To evaluate the effects of gene mutations on Bruton tyrosine kinase inhibitor, zanubrutinib's effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), we examined pooled data from four single-arm studies (BGB-3111-AU-003 [NCT02343120], BGB-3111-207 [NCT03145064], BGB-3111_GA101_Study_001 [NCT02569476], BGB-3111-213 [NCT03520920]; n = 121). Objective response rate (ORR) was higher, though not statistically significant, in patients with activated B-cell-like (ABC)- and unclassified DLBCL (42.9% [21/49]) versus those with germinal-center B-cell-like DLBCL (14.3% [1/7]; p = 0.15). Patients with CD79B mutations had better ORR (60%) versus patients with wild-type alleles (25.9%, p < 0.01). Higher TCL1A expression correlated with better zanubrutinib response (p = 0.03), longer progression-free survival (p = 0.01), and longer overall survival (p = 0.12). TCL1A expression was higher in ABC-DLBCL (p < 0.001) and MYD88/CD79B-mutated subtypes (p < 0.0001). Eighteen patients with high MYC/BCL-2 expression responded better to zanubrutinib (ORR = 61 vs. 29%, p = 0.02). Our results support assessing CD79B mutations, co-expressor DLBCL, and TCL1A expression status to identify patients with DLBCL who will benefit from zanubrutinib. [ABSTRACT FROM AUTHOR]

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort (p < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status. Outcomes analysis revealed similar treatment, response rates, median overall survival, and 1-, 3-, and 5-year survival across all subgroups. Hispanic patients had a 21% lower risk of death (HR = 0.79) than white patients, and Black patients had no significant difference in survival (HR = 0.98). This large retrospective study shows that when standard of care therapy is given within an equal access system, short-term treatment and survival outcomes are the same for all races. [ABSTRACT FROM AUTHOR]

Chidamide (CS055/HBI-8000, tucidinostat) has shown promising effects in the clinical treatment of various hematologic tumors. Diffuse large B-cell lymphoma (DLBCL) has shown highly heterogeneous biological characteristics. There are complex mechanisms of the role of chidamide in DLBCL for in-depth study. It is essential to probe further into the mechanism of drug-tumor interactions as a guide to clinical application and to understand the occurrence and progression of DLBCL. In vitro and in vivo models were utilized to determine the effects of chidamide on signaling pathways involved in the DLBCL tumor microenvironment. The experimental results show that chidamide inhibited the proliferation of DLBCL cell lines in a dose- and time-dependent manner, and down-regulated the expression of NOTCH1 and NFATC1 in DLBCL cells as well as decreased the concentration of IL-10 in the supernatant. In addition, chidamide significantly lowered the expression of PD1 or TIM3 on CD4+T cells and CD8+T cells and elevated the levels of IL-2, IFN-γ, and TNF-α in the serum of animal models, which augmented the function of circulating T cells and tumor-infiltrating T cells and ultimately significantly repressed the growth of tumors. These findings prove that chidamide can effectively inhibit the cell activity of DLBCL cell lines by inhibiting the activation of NOTCH1 and NFATC1 signaling pathways. It can also improve the abnormal DLBCL microenvironment in which immune escape occurs, and inhibit immune escape. This study provides a new therapeutic idea for the exploration of individualized precision therapy for patients with malignant lymphoma. [ABSTRACT FROM AUTHOR]

STOP-CA was a multicenter, double-blind, randomized, placebo-controlled trial comparing atorvastatin to placebo in treatment-naïve lymphoma patients receiving anthracycline-based chemotherapy. We performed a preplanned subgroup to analyze the impact of atorvastatin on efficacy in patients with diffuse large B-cell lymphoma (DLBCL). Patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard doses for six 21-day cycles and were randomly assigned to receive atorvastatin 40 mg daily (n = 55) or placebo (n = 47) for 12 months. The complete response (CR) rate was numerically higher in the atorvastatin arm (95% [52/55] vs. 85% [40/47], p =.18), but this was not statistically significant. Adverse event rates were similar between the atorvastatin and placebo arms. In summary, atorvastatin did not result in a statistically significant improvement in the CR rate or progression-free survival, but both were numerically improved in the atorvastatin arm. These data warrant further investigation into the potential therapeutic role of atorvastatin added to anthracycline-based chemotherapies. [ABSTRACT FROM AUTHOR]

Predicting prognosis is crucial in older patients with diffuse large B-cell lymphoma (DLBCL). This study evaluated the prognostic impact of the controlling nutritional status (CONUT) score, a simple nutritional index, for older DLBCL patients (≥65 years of age) treated with R-CHOP-like regimens in a retrospective, cohort study including 203 patients. The CONUT score was an independent prognostic factor for overall survival (hazard ratio 1.11, 95% confidence interval (CI) 1.01-1.21, p = 0.032) in a multivariable Cox proportional hazards model. On receiver-operating characteristic analysis, the optimal cutoff value was 3. The CONUT score (≥3 or <3) effectively stratified older DLBCL patients, regardless of the International Prognostic Index (p = 0.71 for interaction). Further, the CONUT score independently affected initial dose intensity (odds ratio 0.84, 95% CI 0.73-0.95, p = 0.008), likely reflecting the patients' status at diagnosis and affecting dose adjustments. In conclusion, the CONUT score is associated with a poorer prognosis in older DLBCL patients. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and dependent on angiogenesis (AG), whose main effectors are VEGFA and VEGFR2. Functional single nucleotide variants (SNVs) are described in VEGFA and KDR genes. However, it still unknown whether VEGFA − 2578C/A, −2489C/T, −1154G/A, −634G/C, −460C/T and KDR-604T/C, −271G/A, +1192G/A and +1719A/T SNVs act on DLBCL risk and angiogenic features. Genomic DNA from 168 DLBCL patients and 205 controls was used for SNV genotyping. Angiogenesis was immunohistochemically assessed in tumor biopsies, with reactions for VEGFA, VEGFR2, and CD34. VEGFA –1154GG genotype were associated with 1.6-fold higher DLBCL risk. KDR + 1192GG plus KDR + 1719 TT and KDR + 1192GG plus VEGFA − 2578CC combined genotypes are associated with 2.19- and 2.04-fold higher risks of DLBCL, respectively. VEGFA − 634GG or GC genotypes are associated with increased microvessel density and VEGFA levels. No relationship was observed between SNVs and cell-of-origin classification of DLBCL, but higher VEGFA and VEGFR2 were seen in non-germinal center tumors. [ABSTRACT FROM AUTHOR]

Altered metabolic fingerprints of Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) may offer novel opportunities to identify new biomarkers and improve the understanding of its pathogenesis. This study aimed to investigate the modified metabolic pathways in extranodal, germinal center B-cell (GCB) and non-GCB DLBCL NOS from the head and neck. Formalin-fixed paraffin-embedded (FFPE) tissues from eleven DLBCL NOS classified according to Hans' algorithm using immunohistochemistry, and five normal lymphoid tissues (LT) were analyzed by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Partial Least Squares Discriminant Analysis showed that GCB and non-GCB DLBCL NOS have a distinct metabolomics profile, being the former more similar to normal lymphoid tissues. Metabolite pathway enrichment analysis indicated the following altered pathways: arachidonic acid, tyrosine, xenobiotics, vitamin E metabolism, and vitamin A. Our findings support that GCB and non-GCB DLBCL NOS has a distinct metabolomic profile, in which GCB possibly shares more metabolic similarities with LT than non-GCB DLBCL NOS. [ABSTRACT FROM AUTHOR]

Yet, the description of a polymorphic cell infiltration in LN biopsy, the absence of clinical lymphadenopathy at presentation, the history of psoriatic arthritis as well as the preceded treatment with anti-tumor necrosis factor (TNF)- and cyclosporine raised diagnostic concerns. Although the patient could not finally avoid R-CHOP immunochemotherapy, this case highlights that a trial of NBA withdrawal under very close monitoring could be a rational therapeutic choice even in patients with aggressive ID-LPDs. Keywords: diffuse large B-cell lymphoma; psoriasis; infliximab; apremilast; novel biologic agent; anti-TNF EN diffuse large B-cell lymphoma psoriasis infliximab apremilast novel biologic agent anti-TNF 1695 1700 6 10/12/23 20231001 NES 231001 The association of psoriasis with cancer has been a matter of debate, especially in the era of the novel biologic agents (NBA). Lastly, taking into consideration our case with the re-appearance of the lymphoma despite the change of NBA as well as all the other cases described in Table 1, the appearance of LPDs in psoriatic patients is a more complex process influenced by clinical disease duration and extension, the time length of immunosuppression and the nature of the various treatments administered. [Extracted from the article]

Low-density lipoprotein receptor-related protein-6 (LRP6) is overexpressed in various cancers. The small molecule salinomycin sodium inhibits LRP6. We observed a higher proportion of subjects with non-germinal center B (non-GCB) subtypes having high LRP6 expression than those with GCB subtypes by immunohistochemistry. The PCR and Western blot assays demonstrated increased LRP6 expression in non-GCB subtype cells. In addition, CCK-8 assays and transwell cell migration assays revealed that salinomycin sodium exhibited dose- and time-dependent inhibition of proliferation and migration in non-GCB subtype cells. Furthermore, Western blot assays showed that salinomycin sodium decreased the expression of Bcl2, while increasing the expression of Bax. Additionally, salinomycin sodium suppressed LRP6 expression, blocked LRP6 phosphorylation, and inhibited the Wnt/β-catenin and mTORC1 signaling pathways. Our results suggest that LRP6 is highly expressed in non-GCB subtype. Furthermore, salinomycin sodium inhibited LRP6 expression and the Wnt/β-catenin and mTORC1 signaling in non-GCB subtype cells, and displayed potent anticancer activity. [ABSTRACT FROM AUTHOR]

Upregulation of the anti-apoptotic protein MCL-1 has been implicated in chemotherapy resistance and poor clinical outcomes in B-cell lymphoma (BCL). We report the activity of AMG176, a direct, selective MCL-1 inhibitor, in preclinical models of BCL. A panel of cell lines representing diffuse large B-cell lymphoma (DLBCL), double-hit lymphoma (DHL) and Burkitt's lymphoma (BL) was selected. AMG176 induced apoptotic cell death in a dose- and time-dependent manner in all BCL cell lines. Baseline MCL-1 expression was not predictive of response. AMG176 exhibited impressive synergy with venetoclax and chemotherapeutic agents, less so with proteasomal inhibitors, and antagonism with anti-CD20 monoclonal antibodies. The activity of AMG176 could not be confirmed in murine models of BCL. Combination therapy targeting MCL-1 and BCL-2 may provide an alternative therapeutic approach in BCL, however optimal patient selection will remain the key to obtaining high response rates and tolerability. [ABSTRACT FROM AUTHOR]

TCF3 is a lymphopoietic transcription factor that acquires somatic driver mutations in diffuse large B-cell lymphoma (DLBCL). Hypothesizing that expression patterns of TCF3-regulated genes can inform clinical management, we found that unsupervised clustering analysis with 15 TCF3-regulated genes and eight additional ones resolved local DLBCL cases into two main clusters, denoted Groups A and B, of which Group A manifested inferior overall survival (OS, p = 0.0005). We trained a machine learning model to classify samples into the Groups based on expression of the 23 transcripts in an independent validation cohort of 569 R-CHOP-treated DLBCL cases. Group A overlapped with the ABC cell-of-origin subgroup but its prognostic power was superior. GSEA analysis demonstrated asymmetric expression of 30 gene sets between the Groups, pointing to biological differences. We present, validate and make available a novel method to assign DLBCL cases into biologically-distinct groups with divergent OS following R-CHOP therapy. [ABSTRACT FROM AUTHOR]

This study included 146 primary gastric diffuse large B-cell lymphoma patients. Next-generation RNA sequencing and fluorescent in situ hybridization were performed on tumors from 27 and 38 patients, respectively. Five-year and 10-year overall survival (OS) rates were 77% and 57%, respectively. Lugano and TNM clinical stage were independent survival factors. Tier I mutation was found in 21 patients. The genetic subtypes were A53 (n = 3), MCD (n = 5), BN2 (n = 5), N1 (n = 5), EZB (n = 1), and NOS (n = 8). OS was significantly shorter in high-risk genetic subtypes (A53, MCD, and N1) than low-risk subtypes (BN2, EZB, and NOS). Frequencies of high-risk genetic subtypes were higher in patients with Lugano stage II/IV and TNM clinical stage III + IV than in those with Lugano stage I and TNM clinical stage I + II. Although genetic testing was performed in only a small number of cases, the results suggested that high-risk genetic subtypes were associated with advanced clinical stages and shorter survival. [ABSTRACT FROM AUTHOR]

The clinical significance of extra copy (EC) genotypes of BCL2, MYC, and BCL6 have not been fully elucidated. We evaluated the EC and translocation statuses of BCL2, MYC, and BCL6 in 190 diffuse large B-cell lymphoma (DLBCL) cases using fluorescence in situ hybridization. EC genotype was sub-classified according to copy number-gained tumor cell ratio (EC1, >20% but ≤50%; EC2, >50%). Only the BCL2-EC groups, not MYC-EC or BCL6-EC groups, displayed significantly increased immunoreactivity of the corresponding protein. Moreover, the BCL2-EC2 group was significantly associated with poor overall survival (OS) and progression-free survival (PFS) in a 147 R-CHOP-treated patient subset, which was also statistically significant as per the multivariate survival analysis for PFS. No significant differences in the survival of MYC, BCL6, concurrent BCL2/MYC, BCL6/MYC, BCL2/BCL6, or triple EC groups were observed. BCL2-EC may contribute to increased BCL-2 protein expression and serve as a predictor of treatment outcomes in DLBCL. [ABSTRACT FROM AUTHOR]

This study's focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint. [ABSTRACT FROM AUTHOR]

Secondary central nervous system lymphoma (SCNSL) affects approximately 5% of patients with aggressive large B-cell lymphoma (LBCL) and is associated with poor outcomes. This retrospective, multicenter study included 62 consecutive patients with SCNSL intended for transplant with high-dose methotrexate (HD-MTX)-based induction followed by high-dose thiotepa, busulfan, melphalan, rituximab (TBMR) conditioning and autologous stem cell transplantation (ASCT). Median age was 58 years (range 20–75) and 52 (84%) patients had ECOG performance status >1 at diagnosis of SCNSL. Fifty-two (84%) patients completed induction and proceeded to TBMR/ASCT. With median follow-up 5.7 years, 5-year progression-free and overall survival rates were 53% (95% CI 39–65%) and 65% (95% CI 51–76%) for all patients and 62% (95% CI 45–74%) and 73% (95% CI 57–84%) for those undergoing TBMR/ASCT, respectively. Despite a historically poor prognosis, HD-MTX-based induction followed by TBMR/ASCT has the potential to achieve long-term survival in a substantial proportion of patients with SCNSL. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma is an aggressive disease occurring primarily in elderly patients. Despite high curative rates with doxorubicin-containing treatment, some elderly patients receive less intensive treatments, mainly due to advanced age, comorbidities, and concerns of cardiotoxicity from doxorubicin-containing regimens. We analyzed 1009 patients aged 75 years or older and 10,090 age- and sex-matched comparisons. We aimed to evaluate long-term cardiovascular side effects in elderly patients treated with doxorubicin. Approximately, 64% of patients received doxorubicin-containing treatment. These patients had a persistently increased risk of new-onset heart failure with a hazard ratio of 1.5 and 1.7 when conditioning on survival without heart failure to 6 and 24 months, respectively. Moreover, we observed an increased risk of venous thromboembolism during the first six months following the lymphoma diagnosis. On the contrary, no difference in risk of developing ischemic heart disease or stroke following doxorubicin-containing treatment was observed. [ABSTRACT FROM AUTHOR]

This study compared the real-world healthcare resource utilization (HRU), costs, adverse events (AEs), and AE treatments associated with the chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel), for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Adults with DLBCL who received tisa-cel or axi-cel were identified in the Premier Healthcare Database (2017–2020). Non-CAR-T costs, HRU, and AE rates during the infusion and follow-up periods were compared between the tisa-cel and axi-cel cohorts. Of 119 patients, 33 received tisa-cel (86% as inpatient infusion) and 86 received axi-cel (100% inpatient). Tisa-cel was associated with significantly shorter mean inpatient length of stay than axi-cel during infusion (11.3 vs. 18.3 days) and follow-up ([monthly] 3.9 vs. 6.9 days). Non-CAR-T costs were significantly lower for tisa-cel compared with axi-cel during infusion ($27594.8 vs. $51378.3) and follow-up ([monthly] $28777.3 vs. $46575.7; both p<.05). Rates of AEs and AE treatments were similar. [ABSTRACT FROM AUTHOR]

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis after frontline immunochemotherapy. This retrospective study investigated the effect of consolidative radiation after systemic treatment in newly diagnosed stage I–II de novo CD5+ DLBCL. In this study, 22 patients received consolidative radiotherapy (RT) after immunochemotherapy (chemotherapy + RT group) and 28 patients received chemotherapy alone. Patients who received chemotherapy alone had a significantly shorter PFS and OS than those who received consolidative radiotherapy. The five-year PFS rates for the chemotherapy + RT and chemotherapy alone groups were 75.1% and 40.5%, respectively. The five-year OS rates for the chemotherapy + RT and chemotherapy alone groups were 84.2% and 50.1%, respectively. Even after receiving consolidation radiotherapy, 2/22 (9.1%) patients experienced CNS relapse. Age >60 years and lack of radiotherapy were independent prognostic factors for PFS and OS. Ki-67 (≥80%) was an independent prognostic factor for poor OS. Consolidative radiotherapy might be a good option for stage I-II CD5+ DLBCL, but further investigation is needed. [ABSTRACT FROM AUTHOR]

The activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) has an aggressive course and is associated with poor prognosis in the relapsed or refractory setting. ABC-DLBCL is characterized by chronic active signaling of NF-κB, which is dependent on the CARD11-BCL10-MALT1 (CBM) complex. MALT1 is a key effector of the CBM complex and activates canonical NF-κB and AP-1 among other transcription factors via distinct protease and scaffold functions. There is therefore growing interest in therapeutic targeting of MALT1 for B-cell malignancies. Here, we review recent advances in therapeutic targeting of MALT1 for ABC-DLBCL. Covalent and allosteric MALT1 protease inhibitors have been developed which inhibit growth of ABC-DLBCL in preclinical models, and two clinical MALT1 protease inhibitors are being developed in phase I clinical trials. Importantly, these compounds can overcome resistance to BTK inhibitors in preclinical models. Alternative compounds blocking the scaffold effect of MALT1 are also in early preclinical development. Blockade of MALT1 protease activity may have important implications for anti-lymphoma immunity by increasing immunogenicity of ABC-DLBCL cells and also by potentiating anti-lymphoma activity of other immune cells in the lymphoma microenvironment. Together, early data suggest that MALT1 is a promising target for ABC-DLBCL and possibly other B-cell malignancies, and can have lymphoma cell-intrinsic as well as immune-mediated therapeutic effects. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed for 72 relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients ineligible for autologous stem-cell transplantation (ASCT) treated between 2004 and 2017, efficacy and safety profile of rituximab (375 mg/m2) in combination with etoposide (300 mg/m2) and ifosfamide (1500 mg/m2) at 2, 3, or 4-week intervals. Median age was 79 years (range, 64–92). The median number of previous line was 1 (range 1–8). Patients received a median of six cycles (1–12). Fourteen patients (19%) presented partial and 14 complete responses (19%). Among the 369 cycles, nine patients developed febrile neutropenia (13%), 14 a grade 3–4 neutropenia (19%), 7 a grade 3–4 thrombocytopenia (10%) without grade 3–4 non-hematological toxicity. With a median follow up of 7.8 months, the median progression-free survival, overall survival, and duration of response were 4.4 months, 9.4 months, and 12 months, respectively. This regimen represents a therapeutic option in R/R DLBCL patients ineligible to ASCT. [ABSTRACT FROM AUTHOR]

The utility of circulating tumor DNA (ctDNA) in classifying the cell origin of diffuse large B-cell lymphoma (DLBCL) has not been explored in the Chinese population. In this study, we aimed to investigate the genetic characteristics of DLBCL based on both tumor and ctDNA sequencing and to assess the predictive value of ctDNA in DLBCL. A targeted sequencing panel of 413 genes was applied to tumor biopsies and paired plasma samples obtained from 30 patients with DLBCL before therapeutic intervention (pretreatment). The concordance between plasma genotyping classification and traditional cell-of-origin classification using tumor tissue was 80.0% (20/25). Patients with higher baseline plasma ctDNA levels had poorer survival compared to those with lower ctDNA levels (2-year progression survival rate: 40.0% vs. 80.0%, p = 0.011; 5-year overall survival rate: 30.5% vs. 70.0%, p = 0.004). Collectively, our results demonstrated that pretreatment ctDNA analysis could assist origin determination and prognosis prediction clinically. [ABSTRACT FROM AUTHOR]

Anthracycline-based chemoimmunotherapy with R-CHOP is the standard treatment for diffuse large B-cell lymphoma (DLBCL) but is associated with increased risks of cardiotoxicity. The alternative regimen R-CEOP substitutes etoposide for doxorubicin and is commonly administered to DLBCL patients with cardiovascular comorbidities, although there is limited evidence supporting its use. This multicenter real-world study included 138 consecutive patients with newly-diagnosed DLBCL treated with R-CEOP and 414 patients treated with R-CHOP matched 1:3 for age and International Prognostic Index. With median follow-up time 4.6 years, R-CEOP was associated with significantly inferior 4-year progression-free survival (32 vs. 52%, p < 0.0001), overall survival (39 vs. 59%, p < 0.0001), and disease-specific survival (48 vs. 69%, p < 0.0001) compared to R-CHOP. R-CHOP should remain the preferred regimen for most patients with DLBCL. While R-CEOP may be a reasonable choice for patients strictly ineligible for anthracyclines, the inferior outcomes of this regimen suggest that this high-risk population requires novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) treatments have been rapidly evolving for patients treated in later lines of therapy (LoT). Country-specific cancer registry data for the US and Western Europe (WE) were combined with physician survey results to project the incidence, prevalence, and number of DLBCL and FL patients eligible for and treated by LoT between 2020 and 2025. The total number of incidents and prevalent cases of DLBCL and FL is expected to increase between 2020 and 2025 in the US and WE. 56% and 53% of the third line plus (3L+) eligible DLBCL patients and 60% and 55% of eligible FL patients initiated treatment in the US and WE, respectively. Further research is warranted to understand the reasons behind the high proportion of treatment eligible patients who do not initiate treatment, and potential differences between countries, especially in the 3L + settings. [ABSTRACT FROM AUTHOR]

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments. [ABSTRACT FROM AUTHOR]

Diffuse large-cell B-cell lymphoma (DLBCL) is the most common lymphoid malignancy. About 30–40% of the patients will not be cured by standard Rituximab (R)-CHOP-like immune-chemotherapy, and many of them experience relapse and eventually succumb to their disease. Enhancing first-line efficacy in patients at higher risk, among them many elderly, is key to improve long-term outcomes. Numerous attempts to combine R-CHOP with targeted agents failed in large randomized phase III trials. The addition of Ibrutinib enhanced survival in younger patients, but increased toxicity across all age groups, especially in the elderly. Older DLBCL patients impose particular challenges, since they often present with more advanced disease, and exhibit treatment-relevant comorbidities. ImbruVeRCHOP trial aims at identifying patients who need that benefit from rationally augmented first-line regimens without experiencing overt toxicity and detecting their molecular signatures of response. This first analysis presents encouraging feasibility, safety, and preliminary response data in elderly high-risk DLBCL patients. [ABSTRACT FROM AUTHOR]

Identification of new prognostic factors in relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) is essential for developing risk-adapted approaches. We retrospectively analyzed prognostication based on metabolic tumor volume (MTV) in rel/ref DLBCL (n = 108) before platinum-based salvage chemotherapy. Using 41% SUVmax threshold, patients achieving complete response (CR) exhibited significantly lower baseline values of MTV, compared to those achieving partial response (PR) or with progression of disease (medians MTV 16.26 versus 72.51 versus 98.11 ml, respectively). As a continuous variable, log2(MTV) was predictive of failure to achieve CR (1-unit increase odds ratio [OR] = 1.58, p < 0.001). Log2(MTV) significantly predicted progression-free survival (PFS) and overall survival (OS), and one-unit increase in log2(MTV) was associated with shorter PFS (hazard ratio [HR] = 1.12, p = 0.035) and OS (HR = 1.17, p = 0.007). However, heterogeneity in the selection of post-salvage chemotherapy approaches may have affected survival. These data demonstrate the ability of presalvage MTV to discriminate responders from non-responders to platinum-based chemotherapy and predict survival. [ABSTRACT FROM AUTHOR]

The impact of body mass index (BMI) on survival in lymphoma remains controversial. We leveraged a prospective cohort of lymphoma patients enrolled to SPORE Molecular Epidemiology Resource between 2002 and 2015 to assess the association of BMI before diagnosis, BMI at diagnosis, and BMI change over time with lymphoma-specific survival (LSS). A total of 4009 lymphoma patients (670 diffuse large B-cell lymphoma (DLBCL), 689 follicular lymphoma (FL), 1018 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and 1632 other subtypes) were included. Significantly shorter LSS after diagnosis was observed for FL patients who were obese before diagnosis (HR: 3.02, 95%CI: 1.43–6.41, p=.004) and for those with a ≥ 5% increase in BMI from diagnosis to 3-year follow-up (HR: 3.53, 95%CI: 1.22–10.2, p=.020). In contrast, obesity prior to or at the time of diagnosis was not associated with LSS in DLBCL and CLL/SLL. The impact of weight control after diagnosis in FL patient warrants investigation. [ABSTRACT FROM AUTHOR]

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (p = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT. [ABSTRACT FROM AUTHOR]

Although treatment for diffuse large B-cell lymphoma (DLBCL) has taken some notable steps in the 2000s, there are still subgroups of patients suffering from high mortality and relapse rates. To further improve treatment outcomes, it is essential to discover new mechanisms of chemotherapy resistance and create new treatment approaches to overcome them. In the present study, we analyzed the expression of chemokines and their ligands in systemic and testicular DLBCL. From our biopsy sample set of 21 testicular and 28 systemic lymphomas, we were able to demonstrate chemokine profile differences and identify associations with clinical risk factors. High cytoplasmic CXCL13 expression had correlations with better treatment response, lower disease-related mortality, and limited stage. This study suggests that active CXCR5/CXCL13 signaling could overtake the CXCR4/CXCL12 axis, resulting in a better prognosis. [ABSTRACT FROM AUTHOR]

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is difficult to cure; non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) DLBCL have worse outcomes than GCB DLBCL. Ibrutinib and lenalidomide are synergistic in vitro in ABC DLBCL and may augment salvage chemotherapy. In part 1 of this phase 1b/2 study (NCT02142049), patients with relapsed/refractory DLBCL received ibrutinib 560 mg and escalating doses of lenalidomide on Days 1–7 with DA-EPOCH-R (Days 1–5) in 21-day cycles. In part 1 (N = 15), the maximum tolerated dose was not reached with lenalidomide 25 mg (recommended part 2 dose [RP2D]); most common grade ≥3 adverse events were anemia (73%) and febrile neutropenia (47%); the overall response rate (ORR) was 40%. At the RP2D (n = 26), ORR was 71% in non-GCB and 64% in ABC. Ibrutinib and lenalidomide with DA-EPOCH-R had a manageable safety profile and antitumor activity in relapsed/refractory DLBCL, especially the non-GCB subtype. [ABSTRACT FROM AUTHOR]

To investigate the molecular mechanism of miR-145-5p in diffuse large B-cell lymphoma (DLBCL) tissues and cells. The tissues from patients with DLBCL were collected for RT-qPCR or immunohistochemistry. Cell viability, proliferation, migration, invasion, the relationship between miR-145-5p and S1PR1, and proteins related pathway were detected using CCK-8, BrdU staining, Transwell assay, dual luciferase report assay, and western blotting, respectively. The results showed that miR-145-5p was down-regulated and positively correlated with the survival of DLBCL patients. Overexpression of miR-145-5p inhibited cell proliferation, migration, and invasion in cell model. miR-145-5p directly targeted S1PR1. miR-145-5p down-regulated S1PR1, p-AKT/AKT, and p-STAT3 expression. The reduction of miR-145-5p-induced cell movement was reversed by S1PR1 overexpression. Moreover, S1PR1-induced addition of cell growth was clearly alleviated in LY294002 or S3I-201 treated cells. S1PR1 was up-regulated in the tissues of DLBCL patients. In conclusion, miR-145-5p regulated DLBCL cell growth and movement through suppressing S1PR1/STAT3/AKT pathway. [ABSTRACT FROM AUTHOR]

Positron emission tomography-computed tomography (PET-CT) has become the primary modality for staging in diffuse large B-cell lymphoma (DLBCL), whereas the role of staging bone marrow biopsy (BMB) has become less clear. In this analysis, we included 7,005 DLBCL patients in SEER-Medicare who received either PET-CT without BMB (PET-CT w/o BMB), CT with BMB (CT w/ BMB), or both PET-CT and BMB (PET-CT w/ BMB). The proportion of patients undergoing PET-CT increased across years of diagnosis, while the proportion undergoing CT or BMB decreased. In a fully adjusted Cox proportional hazards model, PET-CT w/ BMB was associated with a marginally superior OS compared to PET-CT w/o BMB. Notably, the association between PET-CT w/ BMB and OS was strongest in patients ≤70 years, but was not present when looking at individual stage of diagnosis. Overall, these data do not provide sufficient support to eliminate staging BMB in patients who undergo PET-CT. [ABSTRACT FROM AUTHOR]

We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7 years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0–1 (smIPI, 58.1%), and had non-bulky disease (<7 cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0–1 versus 2–4 was 89.5% versus 69.7%, respectively (P = 0.005). Bulky disease (≥7 cm) was associated with worse PFS and OS on univariable and multivariable analyses (P < 0.05). Patients with smIPI 0–1 without bulky disease have excellent outcomes. However, patients with smIPI 2–4 or bulky disease have a high risk of progression. [ABSTRACT FROM AUTHOR]

Germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtype diffuse large B-cell lymphoma (DLBCL) showed differential prognosis. Our results suggested that ouabain induced stronger inhibition of growth in Su-DHL4 (GCB), and it triggered obvious apoptosis in Su-DHL4 rather than in OCI-Ly3 (ABC). Two subtype cell lines also showed distinct metabolic phenotypes involving remarkable enrichment of Ribulose-5-Phosphate, hypoxanthine, and guanine in Su-DHL4 cells. Ouabain disturbed metabolic patterns of both cell lines dose-dependently manifested inhibition of free fatty acids and amino acids metabolism, among which ornithine was further identified as potential quantitative marker. Up-regulated Ribulose-5-Phosphate and NADPH/NADP+ level, SOD1, and CAT expression by ouabain enabled OCI-Ly3 cells to resist ROS, while enhanced hypoxanthine and guanine oxidation promoting ROS generation by ouabain, and lowered capacity of scavenging ROS indicated by lowered SOD1 and CAT expression and NADPH/NADP+ levels in Su-DHL4 cells made it more vulnerable to apoptosis through caspase 7 pathway. [ABSTRACT FROM AUTHOR]

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 − 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) has been correlated with virus infection and immunity status. We retrospectively analyzed the association between HBV antibody and DLBCL development in HBsAg- patients. Compared with HBeAb- patients, HBeAb+ patients displayed unique clinical features. HBV antibody-negative patients had better therapeutic efficiency (p <.05). The media progression-free survival (PFS) and overall survival (OS) of HBV antibody-positive group were shorter than the negative group (p <.05). Furthermore, we found positive association between CD21 and HBsAb and their synergistic effect for prognostic predication. Interestingly, the effect of Rituximab in prognostic improvement was more significant in HBV antibody-positive group than negative group. Univariate analysis showed that HBV antibody was independent risk factor for disease prognosis. Altogether, our investigations identified for the first time the close association between HBV antibody and clinical prognosis in DLBCL patients. These findings provide potential biomarker to predict the effect of Rituximab and prognosis in DLBCL patients. [ABSTRACT FROM AUTHOR]

Data on real-world outcomes of axicabtagene ciloleucel (axi-cel) therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL) are limited. In this intent to treat (ITT) analysis, we reviewed records of 38 consecutive patients with R/R LBCL for whom axi-cel was intended. Twenty-seven (71%) patients received axi-cel and 11 (29%) did not. Patients in the non-axi-cel group had a higher hematopoietic cell transplantation comorbidity index (HCT-CI) (median 4 vs. 2, p =.04). Median overall survival for the ITT, axi-cel and non-axi-cel group was 10 (95% CI, 3.7 to 13), 13 (95% CI, 7.7 to N.R.) and 1 (95% CI, 0.4 to 3.7) month(s) respectively. Factors limiting axi-cel use were disease progression, sepsis, manufacturing failure and socioeconomic barrier in 6 (55%), 3 (27%), 1 (9%) and 1 (9%) patient(s) respectively. Additional strategies are needed to ensure all LBCL patients for whom chimeric antigen receptor (CAR) T-cell therapy is prescribed can receive this treatment. [ABSTRACT FROM AUTHOR]