Search

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]

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well‐being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side‐effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real‐time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision‐making and care pathway design. [ABSTRACT FROM AUTHOR]

Summary: Outcome data of patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) beyond the second line are scarce outside of clinical trials. Novel therapies in the R/R setting have been approved based on single‐arm trials, but results need to be contextualized by real‐world outcomes. Medical records from 3753 Danish adults diagnosed with DLBCL were reviewed. Patients previously treated with rituximab and anthracycline‐based chemotherapy who received the third or later line (3 L+) of treatment after 1 January 2015, were included. Only 189 patients with a median age of 71 years were eligible. The median time since the last line of therapy was 6 months. Patients were treated with either best supportive care (22%), platinum‐based salvage therapy (13%), low‐intensity chemotherapy (22%), in clinical trial (14%) or various combination treatments (32%). The 2‐year OS‐/PFS estimates were 25% and 12% for all patients and 49% and 17% for those treated with platinum‐based salvage therapy. Age ≥70, CNS involvement, elevated LDH and ECOG ≥2 predicted poor outcomes, and patients with 0–1 of these risk factors had a 2‐year OS estimate of 65%. Only a very small fraction of DLBCL patients received third‐line treatment and were eligible for inclusion. Outcomes were generally poor, but better in intensively treated, fit young patients with limited disease. [ABSTRACT FROM AUTHOR]

A study published in the British Journal of Haematology examined the impact of COVID-19 on patients with B-cell non-Hodgkin lymphoma (B-NHL) who received bispecific antibodies. The study included 130 Danish patients who were treated with glofitamab or epcoritamab. Of the 43 patients who were infected with COVID-19, the majority were in complete remission at the time of diagnosis. The severity of COVID-19 symptoms varied, with 2 patients experiencing critical symptoms, 2 experiencing severe symptoms, and 30 experiencing non-severe symptoms. Hospitalization was required for 16 patients, and the most common treatments prescribed were sotrovimab and remdesivir. Overall, the study found low mortality rates from COVID-19 infection in patients with B-NHL after bispecific CD20xCD3 therapy. The study also compared the mortality rates of patients who received bispecific antibodies to those treated with CAR-T-cell therapy, finding that bispecific antibody patients had a lower mortality rate. The study concludes that bispecific CD20xCD3 antibodies can be safely prescribed to lymphoma patients who have been vaccinated for COVID-19 with currently circulating virus variants. [Extracted from the article]

ABSTRACT Objectives Methods Results Conclusion Recent front‐line clinical trials used the International Prognostic Index (IPI) to identify trial‐eligible patients with newly diagnosed diffuse large B‐cell lymphoma (DLBCL). However, many IPI‐like variants with improved accuracy have been developed over the years for rituximab‐treated patients.We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low‐risk IPI patients based on POLARIX/EPCORE DLBCL‐2 trial criteria.We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0–1 scores were included. IPI and NCCN‐IPI assigned 33.3% and 11.9% of patients to the low‐risk group, respectively. Shorter 5‐year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low‐risk IPI group compared with low‐risk NCCN‐IPI group. Analyzed models failed to identify true high‐risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL‐2 trial eligibility criteria.True low‐risk patients are more optimal identified by NCCN‐IPI and should be excluded from front‐line clinical trials due to their excellent prognosis. However, additional high‐risk factors besides clinical prognostic models need to be considered when selecting trial‐eligible patients. [ABSTRACT FROM AUTHOR]

AbstractUp 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]

Purpose Patients and Methods Results Conclusion 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.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).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).The present study did not confirm superiority of R‐CHOEP over R‐CHOP for young patients with high‐risk DLBCL. [ABSTRACT FROM AUTHOR]

Primary results (median follow-up, 10.7 months) from the pivotal EPCORE ® NHL-1 study in relapsed or refractory (R/R) large B-cell lymphoma (LBCL) demonstrated deep, durable responses with epcoritamab, a CD3xCD20 bispecific antibody, when used as monotherapy. We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival (PFS) and overall survival (OS) rates were 27.8% and 44.6%, respectively. An estimated 64.2% of complete responders remained in CR at 24 months. Estimated 24-month PFS and OS rates among complete responders were 65.1% and 78.2%, respectively. Of 119 minimal residual disease (MRD)-evaluable patients, 45.4% had MRD negativity, which correlated with longer PFS and OS. CR rates were generally consistent across predefined subgroups: 36% prior chimeric antigen receptor (CAR) T-cell therapy, 32% primary refractory disease, and 37% International Prognostic Index ≥3. The most common treatment-emergent adverse events were cytokine release syndrome (51.0%), pyrexia (24.8%), fatigue (24.2%), and neutropenia (23.6%). These results underscore the long-term benefit of epcoritamab for treating R/R LBCL with deep responses across subgroups, including patients with hard-to-treat disease and expected poor prognosis (ClinicalTrials.gov Registration: NCT03625037)., (© 2024. The Author(s).)