Survival In non-Hodgkin Lymphoma Research Articles

Causal Effects of the Affordable Care Act (ACA) Implementation on Non-Hodgkin's Lymphoma Survival: A Difference-in-Differences Analysis.

Non-Hodgkin's Lymphoma (NHL) accounts for a substantial number of cancer cases in the United States, with a significant prevalence and mortality rate. The implementation of the Affordable Care Act (ACA) has the potential to impact cancer-specific survival among NHL patients by improving access to healthcare services and treatments. This study aims to assess the impact of the implementation of the ACAon cancer-specific survival among patients diagnosed with NHL. In this retrospective analysis, we leveraged data from the Surveillance, Epidemiology, and End Results (SEER) registry to assess the impact of the ACAon cancer-specific survival among NHL patients. The study covered the years 2000-2020, divided into pre-ACA (2000-2013) and post-ACA (2017-2020) periods, with a three-year washout (2014-2016). Using a Difference-in-Differences approach, we compared Georgia (a non-expansion state) to New Jersey (an expansion state since 2014). We adjusted for patient demographics, income, metropolitan status, disease stage, and treatment modalities. Among 74,762 patients, 56.2% were in New Jersey (42,005), while 43.8% were in Georgia (32,757). The pre-ACA period included 32,851 patients (51.7% in Georgia and 56.7% in New Jersey), and 27,447 patients were in the post-ACA period (48.3% in Georgia and 43.4% in New Jersey). The post-ACA period exhibited a 34% survival improvement (OR=0.66, 95% CI 0.58-0.75). ACA implementation was associated with a 16% survival boost among NHL patients in New Jersey (OR=0.84, 95% CI 0.74-0.95). Other factors linked to improved survival included surgery (OR=0.86, 95% CI 0.81-0.91), radiotherapy (OR=0.77, 95% CI 0.72-0.82), and married status (OR=0.67, 95% CI 0.64-0.71). The study underscores the ACA's potential positive impact on cancer-specific survival among NHL patients, emphasizing the importance of healthcare policy interventions in improving patient outcomes.

Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013–2017: A Population-Based Cohort Study

Introduction: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013–December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. Methods: A retrospective, descriptive study of consecutive cases was conducted at Qatar’s NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. Results: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36–95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. Conclusions: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar’s immigration patterns.

Impact of Deployment on Survival in Military Personnel with Non-Hodgkin Lymphoma

Introduction: It is estimated that approximately 3.5 million active duty service members (ADSM) have deployed to Afghanistan and Iraq from 2001-2022. There has been concern about potential exposure to carcinogenic or environmental hazards during overseas deployment. A recent study found ADSM with no prior deployments had an increased risk of cancer mortality compared to those who had served in Operation Iraqi Freedom/Operation Enduring Freedom. Moreover, Nordic personnel with military deployments were also found to have a lower risk of cancer related death when compared to the general population. While there may be a link between potential environmental exposures, there is a lack of data on non-Hodgkin lymphoma (NHL) survival in servicemembers who have previously deployed. Additionally, there are no studies comparing risk of aggressive B-cell lymphoma in these patient populations. Methods: Documented cases of NHL in the DoD's Tumor Registry (Oncolog) from 2001-2022 were obtained. This information was compared to the Defense Manpower Data Center's deployment data and the two datasets were merged. ADSMs and retirees were included; dependents were excluded. A multivariable logistic regression analysis was done to assess the impact of prior deployment on cancer survival in NHL, accounting for age, race, cancer stage, ethnicity, and gender. Results: There were 2,295 servicemembers and retirees diagnosed with NHL from 2001-2022. About 20% had previously deployed (n=467). Median age at diagnosis in those who had deployed was 35 years compared to 54 years for non-deployed (p&amp;lt;0.001). Race, ethnicity, and gender were similar between both arms. Multivariable logistic regression analysis demonstrated prior deployment was associated with better survival after accounting for age, race, stage, ethnicity, and gender (OR 0.63, 95% CI 0.40-0.97, p=0.037). In addition to deployment status, other variables that influenced survival were age (OR 1.04, 95% CI 1.03-1.54, p&amp;lt;0.001), stage (OR 2.92 for stage IV vs. stage I, 95% CI 2.06-4.15, p&amp;lt;0.001), and race (OR 1.97 for black vs. white race, 95% CI 1.37-2.83, p&amp;lt;0.001). To assess whether NHL subtype played a role in these findings, a post-hoc analysis was performed on patients with B-cell NHLs, revealing that ADSM with prior deployment were equally likely to have indolent and aggressive subtypes of B-cell NHL as ADSM who had never deployed. Among personnel with prior deployment, 29.6% and 70.4% had indolent and aggressive B-cell NHLs respectively, compared to 32.9% and 67.1% amongst those who never deployed (p=0.25). Conclusions: Military personnel with NHL who had previously deployed lived longer than those with no prior deployment, even after adjusting for age differences between the two cohorts. These findings are not attributable to B-cell NHL subtype (i.e. deployed personnel did not have more indolent NHLs than non-deployed personnel). These results highlight the healthy deployer effect, in which ADSM who are deployable are required to meet minimum fitness standards, undergo a physical health assessment, and do not have disqualifying comorbidities. This study did not evaluate whether an overseas deployment is associated with an increased risk of NHL, but it does appear to provide evidence that potential deployment-related exposures do not appear to alter the biology or subtype of B-cell NHLs. Disclaimer: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.

Efficacy and Safety of TLR2 Co-Stimulated CAR T Cells in CD19-Positive Lymphoid Malignancies with Central Nervous System Involvement

Background CD19 chimeric antigen receptor (CAR) T cell therapy showed remarkable remission rates in patients with refractory or relapsed (R/R) non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL). However, data on outcomes of CAR T cell therapy for patients with central nervous system (CNS) involvement are limited, as most of them have been excluded from most pivotal CAR-T studies because of concerns about treatment-related neurotoxicity. Here, we show results of a third generation of CD19 CAR T cells for patients with R/R B cell cancers with CNS involvement in a single-center cohort study. Methods A total of 21 patients with R/R B cell malignancies (including ALL and NHL) with CNS involvement were included in this study. Patients derived peripheral lymphocytes were collected through apheresis and lentivirally transduced with a 3 rd generation CAR containing CD28 and TLR2 co-stimulatory domains. The cells were expanded ex vivo and administered in a single infusion (1×10 6 or 2×10 6 CAR T cells per kilogram of body weight) after a conditioning regimen of cyclophosphamide and fludarabine. Results Of the 21 patients with CNS involvement, 11 patients with ALL and 10 with NHL were included in this study, with a data cutoff of July 2023. All 11 patients with ALL had both bone marrow (BM) and cerebrospinal fluid (CSF) involvement. Of the 10 patients with NHL, 5 of the 10 lymphoma patients had parenchyma involvement, 6 patients (6/10) had CSF infiltration and 1 had oculus sinister involvement; the majority of patients (8/10) were diagnosed with secondary CNS lymphoma, whereas 2 patient was primary CNS lymphoma. Of the 21 patients who were treated, the overall response rate (ORR) was 71% (15/21), with 73% (8/11) in ALL and 70% (7/10) in NHL. 67% of patients with ALL (7/11) had a complete remission in both BM and CSF, while 40% of NHL patients (4/10) had a complete response and 30% (3/10) received a partial response. The median overall survival (OS) of ALL was 14.3 months, with a median follow-up of 20.3 months, while the median OS of NHL was not reached with a median follow-up of 14.2 months. Median progression-free survival (PFS) of ALL and NHL were 11.1 months (95% CI, 0.7-29.9 months) and 4.8 months (95% CI, 1.0-15.3 months), respectively (P = 0.84). In the total CNS cohort, cytokine release syndrome (CRS) of any grade was seen in 20 patients (95%), grade 3 in 3 patients (14%). ICANS occurred in 9 patients (42.8%, including 5 ALL and 4 NHL patients), grade 3 in 5 patients (23.8%), and there was no grade 4 event. Median time to ICANS was 5 days (range, 2-10 days) after CAR-T infusion. All the CRS or ICANS were manageable. No significant difference in occurrence of and time to ICANS was seen between ALL and NHL patients (P = 0.22 and 0.96). CAR T cells were identified in CSF of patients following infusion, and the median time to peak CAR T cells in CSF of ALL and NHL were 6.5 days and 10 days post-infusion, respectively (P = 0.141). Median time to last documented follow-up of all patients (alive or dead) was 18.1 months (range 1.0-31.2 months). At the end point of observation, 5 of the 11 ALL patients and 5 of 10 NHL patients were still alive with sustained CR of CNS disease and systemic disease (Figure 1). Conclusion TLR2-costimulated CAR T cell therapy for patients with R/R B cell malignancies with CNS involvement is safe, feasible, and results in high response rates and durable remission in both ALL and NHL patients with CNS disease. The clinical trial was registered at www.clinicaltrials.gov as # NCT04605666.

Development and validation of CT‑based radiomics model of PET-negative residual CT masses: apotential biomarker forpredicting relapse‑free survival innon-Hodgkin lymphoma patients showing complete metabolic response.

PET-negative residual CT masses (PnRCMs) are usually dismissed as nonviable post-treatment lesions in non-Hodgkin lymphoma (NHL) patients showing complete metabolic response (CMR). We aimed to develop and validate computed tomography (CT)-based radiomics model of PET-negative residual CT mass (PnRCM) for predicting relapse-free survival (RFS) in NHL patients showing CMR. A total of 224 patients who showed CMR after completing first-line chemotherapy for PET-avid NHL were recruited for model development. Patients with PnRCM were selected in accordance with the Lugano classification. Three-dimensional segmentation was done by two readers. Radiomic scores (RS) were constructed using features extracted using the Least-absolute shrinkage and selection operator analysis among radiomics features of PnRCMs showing more than substantial interobserver agreement (> 0.6). Cox regression analysis was performed with clinical and radiologic features. The performance of the model was evaluated using area under the curve (AUC). For validation, 153 patients from an outside hospital were recruited and analyzed in the same way. In the model development cohort, 68 (30.4%) patients had PnRCM. Kaplan-Meier analysis showed that patients with PnRCM had significantly (p = 0.005) shorter RFS than those without PnRCM. In Kaplan-Meier analysis, the high RS group showed significantly (p = 0.038) shorter RFS than the low-scoring group. Multivariate Cox regression analysis showed that high IPI score [hazard ratio (HR) 2.46; p = 0.02], treatment without rituximab (HR 3.821; p = 0.019) were factors associated with shorter RFS. In estimating RFS, combined model in both development and validation cohort showed AUC values of 0.81. The combined model that incorporated both clinical parameters and CT-based RS showed good performance in predicting relapse in NHL patients with PnRCM.

Baseline Serum Albumin Levels for Predicting Progression-free Survival in Patients with Non-Hodgkin Lymphoma: A Single-center Prospective Study in Syria

Abstract BACKGROUND AND AIMS: A low baseline serum albumin (SA) level is considered an adverse prognostic indicator of various solid tumors and hematological malignancies. However, studies evaluating the relationship between SA levels and survival in non-Hodgkin lymphoma (NHL) patients are limited in Syria. Thus, this is the first study to assess the impact of baseline SA as an independent prognostic factor on progression-free survival (PFS) over 18 months (1.5 years) in Syrian NHL patients. METHODS: We prospectively analyzed patients diagnosed with de novo NHL who met the inclusion criteria and were admitted to the Chemotherapy and Radiotherapy Center at Tishreen University Hospital (TUH) in Latakia, Syria, between January 2021 and December 2021. The baseline SA concentration was measured. The PFS rate was estimated using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard regression analyses were carried out. RESULTS: Sixty patients in total were included. SA’s optimal cutoff value for survival analysis was 3.95 g/dL, according to the receiver operating characteristic (ROC) curve. Patients were categorized into two groups based on that value, 25 (41.7%) had low (≤3.95 g/dL) and 35 (58.3%) had high SA levels (&gt;3.95 g/dL). The PFS rate for 18 months was 56.7%. Kaplan–Meier curves showed that patients with low SA had a significantly inferior PFS rate (28% vs. 77.1%, P &lt; .001). The independent prognostic significance of SA was verified by multivariate analysis. CONCLUSION: Low baseline SA levels (≤3.95 g/dL) could be a simple and effective factor in predicting poor 18-month PFS in Syrian NHL patients. To verify our findings, more extensive research is advised.

Children's Oncology Group's 2023 blueprint for research: Non-Hodgkin lymphoma.

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now>95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. The goal of the Children' Oncology Group NHL Committee is to identify optimal cures for every child and young adult with NHL (and LCH). Further advances will require creative solutions, including engineering study groups to combine rare populations, biology-based eligibility, alternative endpoints, facilitating international collaborations, and coordinated correlative biology.

Using Machine Learning to Expand the Ann Arbor Staging System for Hodgkin and Non-Hodgkin Lymphoma

The Ann Arbor system is disadvantaged in utilizing information from additional prognostic factors. In this study, we applied the Ensemble Algorithm for Clustering Cancer Data (EACCD) to create a prognostic system for lymphoma that integrates additional prognostic factors. Hodgkin and non-Hodgkin lymphoma survival data were extracted from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute and divided into the training set (131,725 cases) and the validation set (15,683 cases). Five prognostic factors were studied: Ann Arbor stage, type, site, age, and sex. EACCD was applied to the training set to produce a prognostic system, called an EACCD system, for convenience. The EACCD system stratified patients into eight prognostic groups with well-separated survival curves. These eight prognostic groups had significantly higher accuracies in survival prediction than the 24 Ann Arbor substages. A higher-risk group in the EACCD system roughly corresponds to a higher Ann Arbor substage. The proposed system shows a good performance in risk stratification and survival prediction on both the training and the validation sets. The EACCD system expands the traditional Ann Arbor staging system by leveraging additional prognostic information and is expected to advance treatment management for lymphoma patients.

Increased plasma endostatin and GDF15 in indolent non-Hodgkin lymphoma.

Increased microvascular density correlates with more advanced disease and unfavorable overall survival in non-Hodgkin lymphoma (NHL), suggesting that angiogenesis is important for disease progression. However, studies of anti-angiogenic agents in NHL patients, have generally not shown favorable outcomes. The aim of this study was to investigate whether plasma levels of a subset of angiogenesis-associated proteins are increased in indolent B-cell derived NHL (B-NHL) and to investigate whether the levels differ between patients with asymptomatic versus symptomatic disease. Plasma levels of growth differentiation factor 15 (GDF15), endostatin, matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL), long pentraxin 3 (PTX3), and galectin 3 (GAL-3) were measured by ELISA in 35 patients with symptomatic indolent B-NHL, 41 patients with asymptomatic disease, and 62 healthy controls. Bootstrap t-tests were used to assess the relative differences in biomarker levels between groups. Group differences were visualized using a principal component plot. Mean plasma endostatin and GDF15 levels were significantly higher in symptomatic and asymptomatic lymphoma patients than in controls. Symptomatic patients had higher mean MMP9 and NGAL than controls. The finding of increased plasma endostatin and GDF15 in patients with asymptomatic indolent B-NHL suggests that increased angiogenic activity is an early event in indolent B-NHL disease progression.

Evaluation of the clinical characteristics and prognostic factors of gastrointestinal non-Hodgkin lymphoma based on anatomical sites and histological subtype

Background This study aimed to analyze the clinical characteristics and prognostic factors of patients with non-Hodgkin lymphoma (NHL) in the gastrointestinal tract. Methods This study investigated patients (n = 456) with gastrointestinal tract NHL who had been initially treated in our hospital between January 2018 and December 2021. We compared clinical characteristics and prognostic factors according to the anatomic site of involvement and histologic subtypes. Results Gastrointestinal tract involvement was more common in B-cell than T-cell lymphomas (91.7% versus 8.3%). The intestine (n = 237) involvement was more common than the stomach (n = 219). Patients with T-cell lymphoma were more likely to present with advanced disease and B symptoms than B-cell lymphoma. Subgroup survival analysis was conducted for 358 patients whose follow‐up time was more than 2 years, we found that T-cell immunophenotype and elevated serum lactate dehydrogenase (LDH) were independent prognostic factors for survival. Patients with advanced disease were identified as risk factors for relapsed or refractory gastrointestinal tract NHL. Conclusions In our subgroup survival analysis, we found that the survival outcomes demonstrated no significant differences between the stomach and intestinal tract NHL. Serum LDH levels and histologic subtypes were independent prognostic factors for the survival of gastrointestinal tract NHL. Advanced diseases were considered risk factors for relapsed or refractory gastrointestinal tract NHL.

A Novel, Clinically Adaptable Comorbidity Assessment Tool for Non-Hodgkin Lymphoma (NHL), the Three-Factor Risk Estimate Scale (TRES): Analysis of 40,000 Older Adults Enrolled in SEER-Medicare

Introduction Comorbidities impact survival and tolerance of therapy in patients (pts) with NHL. Lack of a standardized measure and the complexity of available scores has hindered the formal assessment of comorbidities in pts with NHL. We previously developed an easy to use comorbidity score in pts with chronic lymphocytic leukemia (CLL), the CLL comorbidity index (CLL-CI; Gordon et al, CCR, 2021). The CLL-CI is scored by assessing medical conditions in vascular, endocrine and upper gastrointestinal categories. Scores range from 0 to 3. The CLL-CI has been validated in independent cohorts of pts with CLL (Rotbain et al, Blood Adv, 2022) but has not been evaluated in other NHL subtypes. We hypothesized that the CLL-CI would be associated with survival in NHL. As this study includes pts with other NHL subtypes, we now call the CLL-CI the three-factor risk estimate scale (TRES). Methods Our study included pts >65 years old diagnosed with NHL between 2008-2017, selected from the SEER-Medicare linked database. TRES score was evaluated in the 12 months preceding NHL diagnosis using ICD-9/10 diagnosis, procedure codes and prescription information from Medicare part A, B and D claims. If one or more medical conditions were present in each category 1 point was assigned for a maximum score of 3. Pts were classified to low (score 0), intermediate (score 1) and high (score 2-3) risk groups. Chi-square or t-test was used to compare pt characteristic distributions. Kaplan-Meier estimate and multivariable Cox regression with competing risk were used to test the association between mortality and TRES score. Results A total of 40,486 pts with median age 77 years (interquartile 71-83) were included. TRES score was low in 41%, intermediate in 37% and high in 22%. Older age, male sex, black race, Hispanic ethnicity, aggressive NHL subtype, no systemic therapy and living in a census tract with lower income or high school graduation rates were all significantly associated with increased TRES score. Being married and living in the West were associated with lower TRES score. Median follow up from NHL diagnosis was 33 months (interquartile, 13-60 months). Compared to low risk pts, higher TRES scores were associated with shorter overall survival (OS; Fig 1A). In multivariable models of OS, hazard ratios (HR) were 1.27 (95%CI 1.23-1.31) for intermediate and 1.68 (95%CI 1.62-1.74) for high risk pts. Male sex (HR 1.27, 95%CI 1.23-1.31), black race (HR 1.17, 95%CI 1.07-1.28), unmarried (HR 1.1, 95%CI 1.07-1.14), living in the South (HR 1.08, 95%CI 1.02-1.14), stage 4 (HR 1.58, 95%CI 1.50-1.67) and older age were independently associated with shorter OS. Living in a census tract with higher income (HR 0.86, 95%CI 0.81-0.90) or high school graduation rates (HR 0.85, 95%CI 0.81-0.90) and receiving chemoimmunotherapy (HR 0.38, 95%CI 0.36-0.40) were independently associated with longer OS. The most common NHL subtypes were CLL (N=11,406), large B cell (DLBCL; N=11,154), follicular (FL; N=5,087), marginal zone (N=3,647), mantle cell (N=1,565), peripheral T cell (N=1,136), cutaneous T cell (N=1,051) and lymphoplasmacytic (N=651). Higher TRES score was associated with shorter OS in all NHL subtypes (p<0.0001). For the most common NHL subtypes: the estimated 3-year OS was 80%, 72% and 61% in CLL; 58%, 47% and 37% in DLBCL; 85%, 75% and 66% in FL: low, intermediate and high TRES scores, respectively. The cause of death was reported and analyzed in 30,155 pts. The most common cause of death was NHL (23.6%, N=7,110). Compared to low risk, higher TRES scores were associated with increased lymphoma specific mortality (LSM; Figure 1B). In multivariable models, HR were 1.10 (95%CI 1.04-1.17) for intermediate and 1.24 (95%CI 1.17-1.33) for high risk pts. TRES score was significantly associated with LSM in the most common NHL subtypes; 3-year LSM rates in CLL were 6.4%, 8.1% and 10% (p=0.015); DLBCL 31.2%, 37.8% and 43.5% (p<0.001); and FL 8.8%, 14.2% and 17.4% (p<0.001) with low, intermediate and high TRES scores, respectively. Conclusion The TRES comorbidity score is a simple to use tool which can be rapidly assessed and is associated with OS and LSM in older adults with NHL-median OS is more than 5 years shorter in pts with a high TRES score. Assessment of the TRES score should be incorporated into the care of older adults with NHL. Future studies are planned to prospectively evaluate the TRES score as a predictive biomarker to guide the treatment of pts with NHL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Disease Characteristics and Treatment Outcomes with HLX01: A Real-World Study in Patients with B-Cell Non-Hodgkin Lymphoma in China

Introduction B-cell non-Hodgkin lymphoma (NHL) is the most common hematological malignancy encompassing heterogenous subtypes (Dotan et al., PT 2010). Rituximab (R) has changed the treatment landscape of NHL; approvals of rituximab biosimilars have improved access to and the affordability of this treatment (Mohammed et al., J Blood Med 2019). HLX01 is the first rituximab biosimilar approved for the treatment of NHL and chronic lymphocytic leukemia in China. In a Phase 3 trial enrolling patients with diffuse large B-cell lymphoma (DLBCL), HLX01 demonstrated bioequivalence to reference rituximab in terms of efficacy and safety (Shi et al., J Hematol Oncol 2020). The current study is an ongoing, observational study with the objectives of characterizing the distribution of B-cell NHL subtypes in patients receiving HLX01 and assessing the effectiveness and safety of HLX01 in patients with B-cell NHL subtypes in a real-world setting in China. Methods This multicenter, real-world study enrolled adult patients with pathologically confirmed B-cell NHL subtypes at 40 hospitals in China. HLX01 (either as monotherapy or combination therapy) was recommended, but the selection of treatment regimen was at the investigator's discretion. The primary endpoint was the distribution of B-cell NHL subtypes in patients receiving HLX01. Secondary endpoints were objective response rate (ORR) and complete response (CR) rate in patients with B-cell NHL and progression-free survival (PFS) and overall survival (OS) rates at 1, 3, and 5 years in subgroups categorized by disease characteristics. Response was evaluated every 6 weeks until disease progression or end of treatment, using the Lugano 2014 criteria. After treatment, disease and survival status were followed up every 2 months. Safety was monitored until 1 month after treatment completion. Here, we report results from baseline to 1-year follow-up. Results Between April 2020 and June 2021, 2053 patients were enrolled; of these patients, 1898 had evaluable efficacy data (full analysis set [FAS]) and 1878 had completed ≥ 5 treatment cycles (per-protocol set [PPS]). Overall, the most common subtype was DLBCL (1231/2053, 60.0%), followed by follicular lymphoma (293/2053, 14.3% [Table 1]). Among patients in the FAS, R-CHOP was the most commonly used regimen (1006/1898, 53.0%). Other regimens included BR (175/1898, 9.2%), R monotherapy (150/1898, 7.9%), R2 (63/1898, 3.3%), R-EPOCH (56/1898, 2.95%), DA-R-EPOCH (48/1898, 2.5%), R-DA-EDOCH (18/1898, 0.95%), R-EDOCH (11/1898, 0.58%), and others (371/1898, 19.5%). In the FAS, 868 (45.7%) patients had CR/CRu (CR + unconfirmed CR) and 883 (46.5%) had partial response, contributing to an ORR of 92.3%; in the PPS, the ORR was 93.2%. In 215 patients with evaluable OS and PFS data, median OS and PFS were not reached, and 1-year OS and PFS rates were 90.7% and 74.4%, respectively. In patients with DLBCL in the FAS, 519 (45.5%) had CR/CRu and the ORR was 91.8%. In 139 evaluable patients with DLBCL, 1-year OS and PFS rates were 91.3% and 75.6%, respectively. The ORRs in most subtypes exceeded 90% (Table 2). Among all patients, 423 (20.6%) experienced adverse events (AEs), most of which were grade 1 or 2 in severity. The most common AEs were decreased white blood cell count (3.9%), decreased neutrophil count (3.5%), and nausea/vomiting (3.3%). Conclusions DLBCL is the most common subtype in HLX01-treated patients with B-cell NHL in China. HLX01 showed clinical benefits with favorable safety profiles in patients with B-cell NHL subtypes in a real-world setting. Clinical trial identification: ChiCTR2000032263. Research funding: None. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of multi-agent systemic therapy on all-cause and disease-specific survival for people living with HIV who are diagnosed with non-Hodgkin lymphoma: population-based analyses from the state of Georgia

For people living with HIV (PLWH) who are subsequently diagnosed with non-Hodgkin lymphoma (NHL), we investigate the impact of standard-of-care (SoC) cancer treatment on all-cause, NHL-specific, and HIV-specific survival outcomes. The focus is on a registry-derived, population-based sample of HIV + adults diagnosed with NHL within 2004–2012 in the state of Georgia. SoC treatment is defined as receipt of multi-agent systemic therapy (MAST). In multivariable survival analyses, SoC cancer treatment is significantly associated with better all-cause and NHL-specific survival, but not better HIV-specific survival across 2004–2017. Having a CD4 count <200 near the time of cancer diagnosis and Ann Arbor stage III/IV disease are associated with worse all-cause and HIV-specific survival; the effects on NHL survival trend negative but are not significant. Future work should expand the geographic base and cancers examined, deepen the level of clinical detail brought to bear, and incorporate the perspectives and recommendations of patients and providers.

Analysis and prediction of relative survival trends in patients with non-Hodgkin lymphoma in the United States using a model-based period analysis method.

BackgroundSurvival rates are usually used to evaluate the effect of cancer treatment and prevention. This study aims to analyze the 5-year relative survival of non-Hodgkin lymphoma (NHL) in United States using population-based cancer registry data.MethodsA period analysis was used to evaluate the improvement in long-term prognosis of patients with NHL from 2004 to 2018, and a generalized linear model was developed to predict the 5-year relative survival rates of patients during 2019–2023 based on data from the SEER database stratified by age, sex, race and subtype.ResultsIn this study, relative survival improved for all NHL, although the extent of improvement varied by sex, age group and lymphoma subtype. Survival improvement was also noted for NHL subtypes, although the extent varied, with marginal-zone lymphoma having the highest 5-year relative survival rate (92.5%) followed by follicular lymphoma (91.6%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (87.3%). Across all subtypes, survival rates were slightly higher in females than in males. Survival rates are lower in the elderly than in the young. Furthermore, the study demonstrated that black patients had lower NHL survival rates than white patients. Survival rates for NHL were higher in rural areas than in urban areas. Patients with extra-nodal NHL had a higher survival rate than patients with nodal NHL.ConclusionOverall, patient survival rates for NHL gradually improved during 2004–2018. The trend continues with a survival rate of 75.2% for the period 2019–2023. Analysis by NHL subtype and subgroups indicating that etiology and risk factors may differ by subtype. Identification of population-specific prevention strategies and treatments for each subtype can be aided by understanding these variations.

Environmental pesticide exposure and non-Hodgkin lymphoma survival: a population-based study

BackgroundThere is evidence indicating that pesticide exposure is a risk factor for non-Hodgkin lymphoma (NHL) development. However, the association between pesticide exposure and NHL survival is not well-established.MethodsUsing the California Cancer Registry, we identified patients with a first primary diagnosis of NHL from 2010 to 2016 and linked these patients with CalEnviroScreen 3.0 to obtain production agriculture pesticide exposure to 70 chemicals from the state-mandated Pesticide Use Reporting (PUR) by census tract from 2012 to 2014. In addition, data from PUR was integrated into a geographic information system that employs land-use data to estimate cumulative exposure to specific pesticides previously associated with NHL (glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt) between 10 years prior up to 1 year after NHL diagnosis. Multivariable Cox proportional hazards regression models were used to evaluate the association between total pesticide exposure from CalEnviroScreen 3.0 and individual pesticide exposure from geographic land use data and lymphoma-specific and overall survival.ResultsAmong 35,808 NHL patients identified, 44.2% were exposed to pesticide in their census tract of residence. Glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt exposure was observed in 34.1%, 26.0%, 10.6%, 14.0%, and 12.8% of NHL patients, respectively. Total pesticide exposure at the time of diagnosis was not associated with lymphoma-specific or overall survival. In addition, no association was consistently found between glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4 dimethylamine salt exposure and lymphoma-specific or overall survival.ConclusionsAlthough we found no consistent associations between agricultural pesticide exposure at the neighborhood level and worse survival, these results provide a platform for designing future studies to determine the association between pesticide and NHL.

Ոչհոջկինյան լիմֆոմաները մանկական տարիքում

Non-Hodgkin lymphoma is a group of cancers which is a third common childhood cancer. Signs and symptoms of non-Hodgkin lymphoma vary depending on the localization and special type of lymphoma. The disease can progress rapidly over days or can progress slowly. Treatment options including chemotherapy, radiotherapy and surgical intervention for non-Hodgkin lymphoma depend on the stage, histopathological type of the disease and chemotherapy response. Due to the modern therapeutic approaches overall survival of non-Hodgkin lymphoma accounted for 80% depending on stage and type of the cancer․

Effect of Pesticide Exposure on Non-Hodgkin Lymphoma Incidence and Survival in California

Introduction:While previous studies propose pesticide exposure to be a risk factor for non-Hodgkin lymphoma (NHL) development, results are inconclusive. In addition, the impact of pesticide exposure on NHL survival is not well-established. Therefore, we identified NHL patients from the California Cancer Registry and linked these patients with the statewide pesticide use reporting database to determine the impact of pesticide exposure on NHL-related incidence and outcomes.Methods:Using the California Cancer Registry, we identified patients with a first primary diagnosis of NHL from 2010-2016 and linked these patients with CalEnviroScreen 3.0 to obtain production agriculture pesticide exposure to 70 chemicals from the state mandated Pesticide Use Reporting (PUR) by census tract from 2012-2014. In addition, data from PUR was integrated into a geographic information system that employs land use data to estimate cumulative exposure to specific pesticides previously associated with NHL (glyphosate, organophosphorus, carbamate, phenoxyherbicide and 2,4-dimethylamine salt) between 10 years prior up to 1 year after NHL diagnosis. SEER*Stat software was used to calculate NHL subtype incidence rates by census tract pesticide use level. Multivariable cox proportional hazards regression models were used to evaluate the impact of total pesticide exposure from CalEnviroScreen 3.0 and individual pesticide exposure from geographic land use data on lymphoma-specific and overall survival.Results:Among 35,808 NHL patients identified, 44.2% were exposed to pesticide in their census tract of residence. Pesticide exposure was higher in Hispanic/Latino (46.5%) and non-Hispanic white (45.6%) then Asian/Pacific Islander (37.2%) and African American (34.9%) patients with NHL. Glyphosate, organophosphorus, carbamate, phenoxyherbicide and 2,4-dimethylamine salt exposure was reported in 34.1%, 26.0%, 10.6%, 14.0% and 12.8% of NHL patients, respectively. Pesticide exposure was not associated with increased NHL incidence by NHL subtype or subgroups defined by sociodemographic factors. Total pesticide exposure at time of diagnosis was not associated with lymphoma-specific or overall survival. In addition, no association was consistently found between glyphosate, organophosphorus, carbamate, phenoxyherbicide and 2,4 dimethylamine salt exposure and lymphoma-specific or overall survival.Conclusion:In this large population-based study of neighborhood agricultural pesticide exposure, pesticide exposure was noted to be prevalent among patients diagnosed with NHL, with high pesticide exposure particularly observed in Hispanics/Latinos and non-Hispanic whites. However, pesticide exposure was not consistently associated with increased NHL incidence or worse NHL lymphoma-specific or overall survival. DisclosuresPoh: Acrotech: Honoraria; Incyte: Research Funding; Morphosys: Consultancy. Tuscano: BMS: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Acrotech: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding.

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Improved Survival in Overweight and Obese Patients with Non-Hodgkin's Lymphoma Treated with Rituximab Containing Chemotherapy for Curative Intent

IntroductionConflicting results have been reported about the association between obesity and survival in diffuse large B-cell lymphoma (DLBCL). Some studies have shown improved survival with increased body mass index (BMI), whereas other studies have not supported this association, making the relationship between body weight and survival in DLBCL unclear. Moreover, many of the earlier studies were based on smaller datasets (sample sizes) and/or patient populations who were not treated with rituximab, making the interpretation of these results less clear in the current Rituximab era. Thus, the aim of this study was to investigate the relationship between BMI and survival in non-Hodgkin lymphoma (NHL) patients treated with rituximab containing chemotherapy in a large population-based database in Ontario, Canada.MethodsWe conducted a population-based retrospective cohort study using an administrative database in the Ontario Cancer Registry (OCR) in Ontario, Canada. Incident cases of aggressive histology lymphoma treated with a rituximab containing chemotherapy regimen for curative intent were captured between January 1st, 2008 and October 31st, 2016 using the database from the New Drug Funding Program in Cancer Care Ontario, which provides universal public funding of rituximab for this indication. Exclusion criteria included patients who were < 18 years of age, had diagnosis of HIV, or received rituximab > 6 months from time of diagnosis. Aggressive histology lymphoma was defined according to morphology codes in the OCR, and included DLBCL and Burkitt lymphoma. BMI at time of diagnosis was calculated by dividing weight in kilogram (Kg) by height in meter (m2). We first categorized subjects according to low BMI (≤25 Kg/m2) and high BMI (>25 Kg/m2), and then by the World Health Organization (WHO) criteria for BMI as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2), overweight (25-29.9 Kg/m2) and obese (≥ 30 Kg/m2) for subsequent analyses. Subjects were followed from time of first treatment until death (all-cause). Cox proportional hazard models were used to estimate the impact of BMI on overall survival, after adjusting for explanatory variables, such as age, sex, rural/urban residence, income quintile, and comorbidities (Charlson Comorbidity Index). Survival was estimated using Kaplan-Meier analysis, and statistical comparisons were made using the log-rank statistic.ResultsA total of 7046 patients with aggressive histology NHL treated with a rituximab containing chemotherapy regimen were identified. After excluding 1,075 patients due to implausible or missing BMI data, 5,971 patients were included in the study cohort (Table 1).Kaplan-Meier analysis demonstrated decreased mortality in the overweight and obese groups, and increased mortality in the underweight group, as compared to normal weight group (Figure 1). Multi-variable analyses revealed that increased BMI had a protective effect on overall survival; the rate of all-cause mortality was lower in the high BMI group (HR 0.82; 95% CI 0.74-0.90) compared to the low BMI group. Furthermore, when BMI was categorized by WHO criteria the rate of all-cause mortality was lower in overweight (HR 0.87; 95% CI 0.78-0.97) and obese (HR 0.77; 95% CI 0.68-0.86) groups compared to the normal weight group (Table 2).When BMI was analyzed as a continuous variable, multivariable analyses revealed that an incremental increase in per unit of BMI was associated with an increased rate of overall survival with a HR of 0.98; 95% CI 0.97-0.99.ConclusionIn the largest cohort to-date and with all patients treated with rituximab containing chemotherapy, we show that increased BMI in patients with aggressive histology NHL is associated with improved survival. Hypotheses for improved survival at higher BMIs include higher cumulative anthracycline doses due to its lipophilic nature, and the ability of overweight and obese patients to tolerate more intense chemotherapy regimens with less dose reductions that is known to improve survival. These results have important implications for NHL patients in North America where two-thirds of the population is overweight or obese, and more research is needed to explore the possible mechanisms of improved survival with increased body weight in NHL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical Characteristics and Outcomes of Hemophagocytic Lymphohistiocytosis-Associated Lymphoma: A Case-Control Study

Introduction :Hemophagocytic lymphohistiocytosis (HLH) is frequently associated with malignancies, specifically with lymphoma. It is an heterogeneous and life-threatening disease. HLH is associated with aggressive lymphomas and a worse outcome (1). There is no consensus about the optimal treatment in this group of patients (2). This study compares the characteristics and outcomes of patients with HLH-associated lymphoma to non-HLH-associated lymphoma; and assess the impact of HLH on the survival of patients with lymphoma.Patients and methods :We included 33 adults (age ≥18 years) from 1998 to 2016, with HLH-associated lymphoma. HLH was diagnosed with 5/8 HLH-04 diagnostic criteria and for lymphomas we used the WHO 2008 classification. to determine if there were differences between lymphoma with or without HLH, a control group of patients diagnosed in the same time period with non-HLH-associated lymphoma (n = 66) was randomly selected. To assess the impact of HLH on overall survival (OS), another matched control group was selected by clinical stage, type of lymphoma and the same chemotherapy regimen (n = 33).Results:The patients with HLH-associated lymphoma were younger (37 vs 54 years, p=0.006). Among the clinical characteristics and laboratory abnormalities, patients with HLH-associated lymphoma presented more frequently with higher fever (100 vs 39.39% p <0.001), hepatomegaly (81.82 vs 30.30%, p <0.001), splenomegaly (81.82 vs 27.27% p <0.001), advanced clinical stages III / IV (90.91 vs 59.09%, p <0.001), B symptoms (96.97 vs 77.77%, p=0.004), cutaneous involvement (33.33 vs 7.58%, p = 0.003), liver disease (51.52 vs. 13.6%, p <0.001), higher ferritin levels (4547 vs 274 ug / L, p <0.001) and more lymphopenia (0.43 vs 1.12x109 / L, p=0.001) (table 1). Patients with HLH-associated lymphoma had a worse 2 year-OS (41 vs. 87.4%, p<0.001). The most common type of HLH-associated lymphoma was T-cell non-Hodgkin's lymphoma (NHL) (54.55%) followed by B-cell NHL (27.27%) and Hodgkin's lymphoma (HL) (18.18%). When comparing patients with non-HLH-associated lymphoma matched by clinical stage, lymphoma type, and treatment with patients with HLH-associated lymphoma, the OS at 2-year was lower in the latter group (41 vs 65%, p = 0.038) figure 1. We analyze by lymphoma subtype, and the presence of HLH had only a significant impact in the T cell NHL survival (2 year-OS of 28.8 vs 55.9%, p = 0.011).Conclusion :HLH is associated with advanced lymphomas in young patients. Our results showed that HLH impacts on the OS in patients with T-cell NHL, but we found no significant different outcomes in patients with B-cell NHL and HL with the presence of HLH. Prospective studies are needed to confirm this results.Bibliography:1.-Parikh SA, Kapoor P. Prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis. Mayo Clin Proc. 2014;89(4): 484-492.2.-Daver N, McClain K. A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer. 2017;00(0):1-12. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.