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]

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]

Currently, the International Prognostic Index (IPI) is the most used and reported model for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). IPI-like variations have been proposed, but only a few have been validated in different populations (e.g., revised IPI (R-IPI), National Comprehensive Cancer Network IPI (NCCN-IPI)). We aimed to validate and compare different IPI-like variations to identify the model with the highest predictive accuracy for survival in newly diagnosed DLBCL patients. We included 5126 DLBCL patients treated with immunochemotherapy with available data required by 13 different prognostic models. All models could predict survival, but NCCN-IPI consistently provided high levels of accuracy. Moreover, we found similar 5-year overall survivals in the high-risk group (33.4%) compared to the original validation study of NCCN-IPI. Additionally, only one model incorporating albumin performed similarly well but did not outperform NCCN-IPI regarding discrimination (c-index 0.693). Poor fit, discrimination, and calibration were observed in models with only three risk groups and without age as a risk factor. In this extensive retrospective registry-based study comparing 13 prognostic models, we suggest that NCCN-IPI should be reported as the reference model along with IPI in newly diagnosed DLBCL patients until more accurate validated prognostic models for DLBCL become available. [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]

For most patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), R-CHOP immunochemotherapy leads to complete remission and 60–70% of patients remain progression-free after 5 years. Given a median age of 65, it is relevant to disentangle how DLBCL and DLBCL therapy influence health care use among the survivors. In this nationwide study, the health care use among Danish DLBCL patients diagnosed in 2007–2015, who achieved complete remission after R-CHOP(-like) therapy, was explored and compared to matched comparators from the Danish general population. The post-remission 5-year risk of hospitalization was significantly higher among DLBCL survivors (55%) compared to matched comparators (49%, P < 0.001). DLBCL survivors had on average 10.3 (9.3–11.3) inpatient bed days within 5 years of response evaluation, whereas matched comparators had 8.4 (7.9–8.8). The rate of outpatient visits was also significantly higher(excluding routine follow-up visits, incidence rate ratio, 1.3, P < 0.001), but translated into only a very small absolute difference of <1 outpatient visits within 5 years between DLBCL survivors (4.2 visits, 95% CI, 4.0–4.4) and matched comparators (3.8 visits, 95% CI, 3.7–3.9). In conclusion, DLBCL survivors have an increased incidence of hospital visits due to a wide range of conditions, but in absolute terms the excess use of health care services in DLBCL survivors was small. [ABSTRACT FROM AUTHOR]

Richter's transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Approximately, 2–10% of patients with CLL develop RT, most often as diffuse large B-cell lymphoma. To assess the incidence of RT, we examined risk factors for RT and death among patients with RT in a nationwide CLL cohort (from 2008 to 2016). Among 3772 patients, 113 had biopsy-proven RT. With a median follow-up of 4.3 years, the 5-year cumulative incidence of RT was 2.8%. Advanced Binet stage (B/C) (p<.001), unmutated IGHV (p<.001), and del(17p) (p<.001) were independently associated with risk of developing RT. Half of the patients with RT (49%) were treatment-naïve prior to transformation and demonstrated longer survival after RT compared to patients previously treated for CLL (6.1 vs. 2.8 years, p=.03). Whether this finding could be explained by a higher proportion of clonally unrelated RT among treatment-naïve patients, remain to be addressed. [ABSTRACT FROM AUTHOR]

The addition of the antibody rituximab to CHOP (R-CHOP) has improved the outcome of diffuse large B-cell lymphoma (DLBCL) and is the current standard of care [[1]]. On the contrary, preliminary results from a trial randomizing stage II-IV DLBCL patients to R-CHOP14 and R-CHOP14 plus additional rituximab on day 8 during the first four treatment cycles did not confirm a benefit of intensified rituximab in male patients [[12]]. Consistent with this study, a more recent Swedish study including >7000 DLBCL patients reported comparable improvements in life expectancy for male and female patients during the rituximab introduction period, although no direct comparison between male and female patients was performed [[15]]. As the survival in the general population is gender-specific (5-year OS, 94% for a female and 90% for a male Danish person aged 65 in 2010), crude OS differences between male and female patients may be sensitive to excess deaths in male patients unrelated to DLBCL. [Extracted from the article]

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]