Type 2 diabetes mellitus compromises the survival of diffuse large B-cell lymphoma patients treated with (R)-CHOP – the PLRG report

Drozd-Sokołowska, Joanna; Zaucha, Jan Maciej; Biecek, Przemysław; Giza, Agnieszka; Kobylińska, Katarzyna; Joks, Monika; Wróbel, Tomasz; Kumiega, Beata; Knopińska‐Posłuszny, Wanda; Spychałowicz, Wojciech; Romejko‐Jarosińska, Joanna; Fischer, Joanna; Wiktor-Jedrzejczak, W; Długosz‐Danecka, Monika; Giebel, Sebastian; Jurczak, Wojciech

doi:10.1038/s41598-020-60565-7

Cited by 13 publications

(10 citation statements)

References 28 publications

(29 reference statements)

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“…12 In an analysis by the Polish Lymphoma Research Group of 469 DLBCL patients treated with CHOP or R-CHOP, diabetic patients had a 15% lower 5-year OS. 13 It has been hypothesized…”

Section: Discussionmentioning

confidence: 99%

Risk factors for cardiovascular events and mortality in patients diagnosed with diffuse large B‐cell lymphoma and treated with anthracyclines

Diamond

Ayyappan

Cao

et al. 2022

Hematological Oncology

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There is an increased risk of congestive heart failure (CHF) following anthracyclinebased chemotherapy in patients with Diffuse Large B-cell lymphoma (DLBCL). Little is known about risk factors of CHF, other cardiovascular events (CVE), and CVE effect on outcomes. We conducted a retrospective review of 463 newly diagnosed DLBCL patients treated between 2002 and 2016 with anthracycline containing regimens. At a median follow up of 71.3 months, 10.4% patients developed new CHF, 4.97% had new atrial fibrillation and 3.2% had new coronary artery disease. Age over 65, advanced stage DLBCL and diabetes were associated with increased cumulative incidence of CVE. Patients with prior diabetes had decreased progression-free survival and overall survival in comparison to non-diabetics. Patients who had a CVE in the first year had significant worse OS then patients who did not have a CVE (Hazard Ratio 10.0, 95% CI, 7.24-13.88). A risk score incorporating age at DLBCL diagnosis, baseline lymphocyte count, disease stage and diabetes stratified into groups with low, intermediate and high risk for CVE, with 1year cumulative incidence of CVE of 5.3%, 7.9% and 13.4%. Diffuse large B-cell lymphoma patients treated with anthracycline containing regimens have high incidence of CVE, which are not limited to CHF. Clinical variables at the time of diagnosis can identify the group of DLBCL patients at highest risk of CVE, for whom preventive interventions should be considered. K E Y W O R D S cardiac toxicity, cardiovascular events, diabetes, diffuse large B cell lymphoma | INTRODUCTIONAnthracycline-containing chemoimmunotherapy can achieve high response rates and improve survival in diffuse large B-cell lymphoma (DLBCL), but can cause cardiovascular toxicity. There is an increased risk of congestive heart failure (CHF) following anthracycline treatment, with a dose dependent risk increase. 1,2 This understanding has led to recommended maximum cumulative doxorubicin (or equivalent) dose of 500 mg/m2, with doses frequently limited to 450 mg/m2 in clinical practice. 3 Despite dosing limits, a recent metaanalysis identified a pooled proportion for developing CHF of 4.62%. 4 When the analysis was limited to studies including post treatment cardiac evaluation, the pooled proportion was 11.7%. Cardiac toxicity was increased in studies where the median age was >65 years and including a larger proportion of women. Other than CHF, there are limited data regarding the risk of developing other types of

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“…12 In an analysis by the Polish Lymphoma Research Group of 469 DLBCL patients treated with CHOP or R-CHOP, diabetic patients had a 15% lower 5-year OS. 13 It has been hypothesized…”

Section: Discussionmentioning

confidence: 99%

Risk factors for cardiovascular events and mortality in patients diagnosed with diffuse large B‐cell lymphoma and treated with anthracyclines

Diamond

Ayyappan

Cao

et al. 2022

Hematological Oncology

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“…The four selected risk features have also consistently been found to be independently associated with reduced OS in DLBCL. [22][23][24][25] Although further research is certainly warranted, these reports further underpin the predictor selection proposed in this analysis.…”

Section: Discussionmentioning

confidence: 79%

TRAIL Score: A Simple Model to Predict Immunochemotherapy Tolerability in Patients With Diffuse Large B-Cell Lymphoma

Harris¹,

Bataillard

Choi³

et al. 2022

JCO Clinical Cancer Informatics

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PURPOSE Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) represents the standard of care for first-line treatment of diffuse large B-cell lymphoma (DLBCL). However, many patients are unable to tolerate R-CHOP and have inferior outcomes. This study aimed to develop a practical tool to help physicians identify patients with newly diagnosed DLBCL unlikely to tolerate a full course of R-CHOP. METHODS We developed a predictive model (Tolerability of R-CHOP in Aggressive Lymphoma [TRAIL]) on the basis of a training data set from the phase III GOYA trial (obinutuzumab with CHOP v R-CHOP in 1L DLBCL) using a composite binary end point, identifying patients who prematurely stopped or required reductions of R-CHOP. Candidate predictive variables were selected on the basis of known baseline characteristics that contribute to patient frailty, comorbidity, and/or chemotherapy toxicity. TRAIL was developed using an iterative trial-and-error modeling process to fit a logistic regression model. The final model was evaluated for robustness using a GOYA holdout data set and the phase III MAIN (R-CHOP with or without bevacizumab in 1L DLBCL) R-CHOP-21 data set as external validation. RESULTS TRAIL includes four simple predictors available in the routine clinical setting: Charlson Comorbidity Index, presence of cardiovascular disease or diabetes, serum albumin, and creatinine clearance. Model generalization performance estimated by the area under the curve was around or above 0.70 across GOYA training, GOYA holdout, and MAIN data sets. Classifying patients into low-, intermediate- and high-risk categories, the proportion of patients experiencing a tolerability event was 3.3%, 12.4%, and 32.9%, respectively, in GOYA holdout, and 9.7%, 9.7%, and 34.2%, respectively, in MAIN. CONCLUSION TRAIL may be useful as a clinical decision support tool for treatment decisions in patients with DLBCL who may not tolerate standard chemoimmunotherapies.

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“…Other recently reported studies have shown that a diagnosis of type 2 diabetes is associated with worse outcomes in the context of DLBCL [ 46 , 47 ]; however, sex-specific differences have not been previously reported. In this study, a diagnosis of diabetes had a significant negative impact on male OS ( p = 0.004).…”

Section: Discussionmentioning

confidence: 97%

Metabolic Biomarkers Assessed with PET/CT Predict Sex-Specific Longitudinal Outcomes in Patients with Diffuse Large B-Cell Lymphoma

Jaswal

Sanders

Pullarkat

et al. 2022

Cancers

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In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion.

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Type 2 diabetes mellitus compromises the survival of diffuse large B-cell lymphoma patients treated with (R)-CHOP – the PLRG report

Cited by 13 publications

References 28 publications

Risk factors for cardiovascular events and mortality in patients diagnosed with diffuse large B‐cell lymphoma and treated with anthracyclines

Risk factors for cardiovascular events and mortality in patients diagnosed with diffuse large B‐cell lymphoma and treated with anthracyclines

TRAIL Score: A Simple Model to Predict Immunochemotherapy Tolerability in Patients With Diffuse Large B-Cell Lymphoma

Metabolic Biomarkers Assessed with PET/CT Predict Sex-Specific Longitudinal Outcomes in Patients with Diffuse Large B-Cell Lymphoma

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