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Purpose: Etoposide to standard R‐CHOP is used for high‐risk diffuse large B‐cell lymphoma (DLBCL) in some countries. Due to the lack of randomized trials, a real‐world data study using matching methods was used to test the potential effectiveness of R‐CHOEP over R‐CHOP. Patients and Methods: This study included patients from the Danish Lymphoma Register diagnosed between 2006 and 2020 at the age of 18–60 years with de novo DLBCL and age‐adjusted IPI ≥2. R‐CHOEP treated patients were matched 1:1 without replacement to R‐CHOP treated patients using a hybrid exact and genetic matching technique. Primary endpoints were progression‐free survival (PFS) and overall survival (OS). Results: In total, 396 patients were included; 213 received R‐CHOEP and 183 received R‐CHOP. Unadjusted 5‐year PFS and OS for R‐CHOEP were 69% (95% Confidence intervals [CI]; 63%–76%) and 79% (CI;73%–85%) versus 62% (CI;55%–70%) and 76% (CI;69%–82%) for R‐CHOP (log‐rank test, PFS p =.25 and OS p =.31). A total of 127 patients treated with R‐CHOEP were matched to 127 patients treated with R‐CHOP. Matching‐adjusted 5‐year PFS and OS were 65% (CI; 57%–74%) and 79% (CI; 72%–84%) for R‐CHOEP versus 63% (CI; 55%–73%) and 79% (CI;72%–87%) for R‐CHOP (log‐rank test, PFS p =.90 and OS p =.63). Conclusion: The present study did not confirm superiority of R‐CHOEP over R‐CHOP for young patients with high‐risk DLBCL. [ABSTRACT FROM AUTHOR]

Background: Several clinical prognostic models for diffuse large B‐cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN‐IPI), and models incorporating beta‐2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood. Methods: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. Results: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN‐IPI performed better than the International Prognostic Indexes (IPI, age‐adjusted IPI, and revised IPI). Five‐year overall survival for high‐ and low‐risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN‐IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M‐NCCN‐IPI) by adding β2M to NCCN‐IPI (c‐index 0.708) with improved discriminatory ability compared to NCCN‐IPI (c‐index 0.698, p < 0.05) and 5‐year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high‐intermediate, low‐intermediate and low‐risk group, respectively. Conclusion: International Prognostic Indices, except for NCCN‐IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN‐IPI and should be re‐evaluated in the development setting of future models for DLBCL. [ABSTRACT FROM AUTHOR]

Summary: Cardiovascular diseases, especially congestive heart failure (CHF), are known complications of anthracyclines, but the risk for patients undergoing high‐dose chemotherapy and autologous stem cell transplant (HDT‐ASCT) is not well established. With T‐cell therapies emerging as alternatives, studies of long‐term complications after HDT‐ASCT are warranted. Danish patients treated with HDT‐ASCT for aggressive lymphoma between 2001 and 2017 were matched 1:5 on sex, birth year and Charlson comorbidity score to the general population. Events were captured using nationwide registers. A total of 787 patients treated with HDT‐ASCT were identified. Median follow‐up was 7.6 years. The risk of CHF was significantly increased in the HDT‐ASCT population compared to matched comparators with an adjusted hazard ratio (HR) of 5.5 (3.8–8.1). The 10‐year cumulative incidence of CHF was 8.0% versus 2.0% (p < 0.001). Male sex, ≥2 lines of therapy, hypertension and cumulative anthracycline dose (≥300 mg/m2) were risk factors for CHF. In a separate cohort of 4089 lymphoma patients, HDT‐ASCT was also significantly associated with increased risk of CHF (adjusted HR of 2.6 [1.8–3.8]) when analysed as a time‐dependent exposure. HDT‐ASCT also increased the risk of other cardiac diseases. These findings are applicable for the benefit/risk assessment of HDT‐ASCT versus novel therapies. [ABSTRACT FROM AUTHOR]

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in the western world. It is highly heterogeneous with a variable clinical course, but curable with chemo‐immunotherapy in up to 70% of all cases. The lymphoma presents in lymph nodes and/or extranodal lymphoid tissue, and the diagnosis is based on invasive procedures for histopathologic evaluation. Methods: In this technical study, we evaluated cell‐free DNA (cfDNA) from blood plasma to detect clonal B cells in patients with DLBCL using rearranged immunoglobulin heavy chain gene as targets by next‐generation sequencing. Clonal B cell sequences and frequencies were determined from blood plasma cfDNA and cellular DNA from matched excised lymphoma tissues and mononuclear cells isolated from diagnostic bone marrow and blood samples from 15 patients. Results: We showed that identical clonal rearrangements could be detected in blood plasma and excised lymphoma tissue and that plasma cfDNA was superior in detecting clonal rearrangements compared to blood or bone marrow‐derived cellular DNA. Conclusion: These findings consolidate the role of blood plasma as a reliable and easily accessible source for detecting neoplastic cells in DLBCL. [ABSTRACT FROM AUTHOR]

Purpose: Many patients diagnosed with lymphoma are of working age. Cancer patients are known to have a higher risk of sick leave and disability pension, but this has only been delineated for certain subtypes of lymphoma. Therefore, this study aimed at investigating the overall risk of disability pension for all lymphoma subtypes and at quantifying return to work for patients with lymphoma in work before diagnosis. Patients and Methods: Patients aged 18– 60 years with lymphoma in complete remission (CR) diagnosed between 2000 and 2019 were included in the study. Using national registers, each patient was matched with five comparators from the general population with same sex, birth year, and level of Charlson Comorbidity Index. Risk of disability pension was calculated from 90 days after CR or end of treatment with competing events (death, retirement pension, early retirement pension, relapse for patients, or lymphoma diagnosis for comparators). Return to work for patients was calculated annually until 5 years after diagnosis for patients employed before diagnosis. Results: In total, 4072 patients and 20,360 comparators were included. There was a significant increased risk of disability pension for patients with all types of lymphoma compared to the general population (5-year risk difference: 5.3 (95% confidence interval (CI): 4.4;6.2)). Patients with non-Hodgkin lymphoma were more likely to get disability pension than patients with Hodgkin lymphoma (sex- and age-adjusted 10-year risk difference: 2.9 (95% CI: 0.3;5.5)). One year after diagnosis, 24.5% of the relapse-free patients were on sick leave. Return to work was highest 2 years after diagnosis (82.1%). Conclusion: Patients with lymphoma across all subtypes have a significantly higher risk of disability pension. Return to work peaks at 2 years after diagnosis. [ABSTRACT FROM AUTHOR]

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0–90, 91–365, and +365-day survival. Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0–90 day period, but also up to one year after the diagnosis. For day 0–90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18–32 g/L) contributed to the worse prognosis. Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability. The amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma. It was especially the lower quartile of the PA level (18–32 g/L) that contributed to the worse prognosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Accurate prevalence estimates of diffuse large B‐cell lymphoma (DLBCL) are important for numerous purposes including orphan drug designation. A key criterion for orphan drug designation is a disease prevalence of less than 5/10,000 persons. The objective is to apply and compare different methods of prevalence assessment.In the present nationwide Danish cohort study, the prevalence of DLBCL was assessed using different methodologies, including register‐based and formula‐based approaches.The prevalence calculations were based on 9,492 patients diagnosed with DLBCL since year 2000. Incidence increased and survival improved in the period, resulting in higher prevalence of DLBCL. In year 2023, the 2‐,3‐,5‐,10‐, and 20‐year prevalences were 1.53, 2.19, 3.45, 6.08, and 8.80 per 10,000 adults using the register‐based approach. The formula‐based approach was generally accurate when using restricted mean survival. However, when using median survival, the total prevalence was estimated at 8.1 per 10,000 adults. Furthermore, when extrapolating the median survival from the 5‐year survival under constant hazard assumption as done in some orphan drug designation reports, the prevalence was estimated at 6.6 per 10,000 adults.In conclusion, the estimated DLBCL prevalences are sensitive to the applied method. DLBCL would disqualify from orphan drug designation in some of the mentioned scenarios. [ABSTRACT FROM AUTHOR]

Background and Aim: Based on advances in the diagnosis, classification, and management of diffuse large B-cell lymphoma (DLBCL), a number of new prognostic models have been proposed. The aim of this study was to review and compare different prognostic models of DLBCL based on the statistical methods used to evaluate the performance of each model, as well as to analyze the possible limitations of the methods. Methods and Results: A literature search identified 46 articles that proposed 55 different prognostic models for DLBCL by combining different clinical, laboratory, and other parameters of prognostic significance. In addition, six studies used nomograms, which avoid risk categorization, to create prognostic models. Only a minority of studies assessed discrimination and/or calibration to compare existing models built upon different statistical methods in the process of development of a new prognostic model. All models based on nomograms reported the c-index as a measure of discrimination. There was no uniform evaluation of the performance in other prognostic models. We compared these models of DLBCL by calculating differences and ratios of 3-year overall survival probabilities between the high- and the low-risk groups. We found that the highest and lowest ratio between low- and high-risk groups was 6 and 1.31, respectively, while the difference between these groups was 18.9% and 100%, respectively. However, these studies had limited duration of follow-up and the number of patients ranged from 71 to 335. Conclusion: There is no universal statistical instrument that could facilitate a comparison of prognostic models in DLBCL. However, when developing a prognostic model, it is recommended to report its discrimination and calibration in order to facilitate comparisons between different models. Furthermore, prognostic models based on nomograms are becoming more appealing owing to individualized disease-related risk estimations. However, they have not been validated yet in other study populations. [ABSTRACT FROM AUTHOR]

We investigated if survival was predicted by nadir neutrophil counts after the first cycle of R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Neutrophil counts (109/L) were categorized in four grades in the nadir time frame. Prognostic indices and comorbidity levels were calculated and used to adjust the Cox regression model. Kaplan–Meier and Cox regression methods were used to estimate and compare survival. We identified 965 patients. Grade 4 neutropenia was present in 432 (45%). Grade 0 patients had a 5-year overall survival of 67%, grade 1–2: 78%, grade 3: 64%, and grade 4: 57%. Compared with grade 0 adjusted hazard ratios (HR) for death were: 0.77 (95% CI 0.49–1.21) for grade 1–2, 1.18 (95% CI 0.82–1.71) for grade 3, and 1.33 (95% CI 1.02–1.73) for grade 4. Grade 4 neutropenia after the 1st cycle of chemotherapy predicted inferior outcome compared with grade 0 and 1–2. Grade 1–2 neutropenia seemed to have superior outcome. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary hypertension (PH) has been reported to be associated with myeloproliferative neoplasms (MPN), affecting 5%‐48% of MPN patients. With the aims to describe the prevalence of PH in Ph‐MPN patients and explore the cause in identified subjects, we performed a prospective cohort study of Ph‐MPN patients. Method: Transthoracic echocardiography (TTE) was performed on all patients. When the TTE was abnormal, further investigations were performed according to current guidelines from the European Society of Cardiology. The primary endpoint was the frequency of PH. The secondary endpoint was causes of PH. Results: We included 158 patients, median age was 65 years. Fifty percent had polycythemia vera, 34% essential thrombocytosis, and 11% primary myelofibrosis, 3% post‐ET‐myelofibrosis, and 2% post‐PV‐myelofibrosis. Only six patients (3.8%) were found to have a high probability of PH. They were all examined with right heart catheterization and all met the invasive criteria for PH. In all six patients other causes than MPN for PH were identified, although some contribution from the MPN could not be ruled out in three patients. Conclusion: In the largest study ever reported, we found a lower prevalence of PH (3.8%) than previously reported. Screening for PH in unselected MPN patients is not justified. [ABSTRACT FROM AUTHOR]