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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]

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]

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8 cycles of CHOP(-like) therapy and 22% received 3-4 cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4 cycles vs. 6-8 cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4 cycles versus 6-8 cycles of CHOP(-like) therapy were comparable., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)