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Up 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]

We investigated trends of survival in a population-based cohort study of all 181 adults who received HCT for ALL in Denmark between 2000–2019. Patients had a median (min–max) age of 36 (18–74) years at HCT and were followed for a median of eight years. Overall survival (OS) improved over time with an estimated 2-year OS of 49% (CI 27–66%) in year 2000 versus 77% (CI 59–88%) in year 2019. More patients achieved cure over time (OR for cure per year 1.07, CI 1.00–1.15), while the rate of death in non-cured patients remained stable (HR of excess mortality per year 0.99, CI 0.93–1.06). Relapse decreased over time (HR 0.92 per year, CI 0.87–0.98), whereas non-relapse mortality did not change notably (HR 0.98 per year, CI 0.93–1.04). In conclusion, survival after HCT in adults with ALL has improved over the past two decades, primarily due to more patients achieving cure. [ABSTRACT FROM AUTHOR]

In a recent study by our group we showed a disappointing absence of survival improvement among elderly acute myeloid leukemia (AML) patients from 2001 until 2016. Treatment intensity and survival trends among real-world elderly AML patients diagnosed in the period 2001-2016: a Danish nationwide cohort study However, only 20% of real-world AML patients >70 are alive 1-year after the diagnosis, which emphasizes that novel treatment modalities are urgently needed to improve OS for AML patients of high age. [Extracted from the article]

High-dose prednisolone is used in first-line treatment for lymphoma, but the potential adverse impact on bone health is unclear. Danish patients with diffuse large B-cell lymphoma or follicular lymphoma diagnosed between 2000 and 2012 were matched to the background population. Osteoporotic events (osteoporosis treatment or low-energy fracture) were identified using the Danish National Patient Registry and Prescription Registry. In total, 2589 patients and 12,945 controls were included. Lymphoma patients had increased risk of osteoporotic events compared to the matched population (hazard ratio 1.61 [95% confidence interval 1.40;1.84]). The 5- and 10-year cumulative risks of osteoporotic events for lymphoma patients were 10.0% [8.6;11.4] and 16.3% [13.8;18.7], whereas corresponding risks in the background population were 6.8% [6.3;7.3] and 13.5% [12.4;14.6]. Patients without osteoporotic event in the first two years after treatment were not at higher risk of osteoporotic events in subsequent years. Risk factors for osteoporotic events were female sex and age >70 years. [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]

Treatment of diffuse large B-cell lymphoma (DLBCL) with R-CHOP(-like) regimens include large cumulative doses of prednisolone. In this retrospective study, we evaluated changes in vertebral bone density (VD) in DLBCL patients by measuring CT-ascertained Hounsfield units (HU) at the L3 level. In total, 111 patients diagnosed from 2007 to 2012 and response assessed following first line treatment were included. Post-treatment VD was significantly reduced to 86% of pretreatment VD on average (p < .001). Neither female sex nor high age (>70 years) were significantly associated with greater post-treatment VD reduction. Two years after completing R-CHOP treatment, VD remained significantly lower than baseline VD (p < .001). Vertebral compression fractures visualized by CT were found in 16/111 patients (14%) during follow-up. In conclusion, bone mineral density is significantly reduced following R-CHOP(-like) treatment and vertebral compression fractures are common. Glucocorticoid-induced osteoporosis may therefore have impact on survivorship for the large fraction of DLBCL patients with durable remissions. [ABSTRACT FROM PUBLISHER]