Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: a population-based study.

BACKGROUND: Mental health disorders can potentially decrease quality of life and survival in patients with cancer. Little is known about the survival implications of mental health disorders in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the effect of pre-existing depression, anxiety, or both on survival in a US cohort of older patients with DLBCL. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients aged 67 years or older, diagnosed with DLBCL in the USA between Jan 1, 2001, and Dec 31, 2013. We used billing claims to identify patients with pre-existing depression, anxiety, or both before their DLBCL diagnosis. We compared 5-year overall survival and lymphoma-specific survival between these patients and those without pre-existing depression, anxiety, or both using Cox proportional analyses, adjusting for sociodemographic and clinical characteristics, including DLBCL stage, extranodal disease, and B symptoms. FINDINGS: Among 13 244 patients with DLBCL, 2094 (15·8%) had depression, anxiety, or both disorders; 6988 (52·8%) were female, and 12 468 (94·1%) were White. The median follow-up for the cohort was 2·0 years (IQR 0·4-6·9 years). 5-year overall survival was 27·0% (95% CI 25·1-28·9) for patients with these mental health disorders versus 37·4% (36·5-38·3) for those with no mental health disorder (hazard ratio [HR] 1·37, 95% CI 1·29-1·44). Although survival differences between mental health disorders were modest, those with depression alone had the worst survival compared with no mental health disorder (HR 1·37, 95% CI 1·28-1·47), followed by those with depression and anxiety (1·23, 1·08-1·41), and then anxiety alone (1·17, 1·06-1·29). Individuals with these pre-existing mental health disorders also had lower 5-year lymphoma-specific survival, with depression conferring the greatest effect (1·37, 1·26-1·49) followed by those with depression and anxiety (1·25, 1·07-1·47) and then anxiety alone (1·16, 1·03-1·31). INTERPRETATION: Pre-existing depression, anxiety, or both disorders present within 24 months before DLBCL diagnosis, worsens prognosis for patients with DLBCL. Our data underscore the need for universal and systematic mental health screening for this population, as mental health disorders are manageable, and improvements in this prevalent comorbidity might affect lymphoma-specific survival and overall survival. FUNDING: American Society of Hematology, National Cancer Institute, Alan J Hirschfield Award.

Association of Preexisting Heart Failure With Outcomes in Older Patients With Diffuse Large B-Cell Lymphoma.

Importance: Anthracycline-containing regimens are highly effective for diffuse large B-cell lymphoma (DLBCL); however, patients with preexisting heart failure (HF) may be less likely to receive anthracyclines and may be at higher risk of lymphoma mortality. Objective: To assess the prevalence of preexisting HF in older patients with DLBCL and its association with treatment patterns and outcomes. Design, Setting, and Participants: This longitudinal cohort study used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry from 1999 to 2016. The SEER registry is a system of population-based cancer registries, capturing more than 25% of the US population. Linkage to Medicare offers additional information from billing claims. This study included individuals 65 years and older with newly diagnosed DLBCL from 2000 to 2015 with Medicare Part A or B continuously in the year prior to lymphoma diagnosis. Data were analyzed from September 2020 to December 2022. Exposures: Preexisting HF in the year prior to DLBCL diagnosis ascertained from billing codes required one of the following: (1) 1 primary inpatient discharge diagnosis, (2) 2 outpatient diagnoses, (3) 3 secondary inpatient discharge diagnoses, (4) 3 emergency department diagnoses, or (5) 2 secondary inpatient discharge diagnoses plus 1 outpatient diagnosis. Main Outcomes and Measures: The primary outcome was anthracycline-based treatment. The secondary outcomes were (1) cardioprotective medications and (2) cause-specific mortality. The associations between preexisting HF and cancer treatment were estimated using multivariable logistic regression. The associations between preexisting HF and cause-specific mortality were evaluated using cause-specific Cox proportional hazards models with adjustment for comorbidities and cancer treatment. Results: Of 30 728 included patients with DLBCL, 15 474 (50.4%) were female, and the mean (SD) age was 77.8 (7.2) years. Preexisting HF at lymphoma diagnosis was present in 4266 patients (13.9%). Patients with preexisting HF were less likely to be treated with an anthracycline (odds ratio, 0.55; 95% CI, 0.49-0.61). Among patients with preexisting HF who received an anthracycline, dexrazoxane or liposomal doxorubicin were used in 78 of 1119 patients (7.0%). One-year lymphoma mortality was 41.8% (95% CI, 40.5-43.2) with preexisting HF and 29.6% (95% CI, 29.0%-30.1%) without preexisting HF. Preexisting HF was associated with higher lymphoma mortality in models adjusting for baseline and time-varying treatment factors (hazard ratio, 1.24; 95% CI, 1.18-1.31). Conclusions and Relevance: In this study, preexisting HF in patients with newly diagnosed DLBCL was common and was associated with lower use of anthracyclines and lower use of any chemotherapy. Trials are needed for this high-risk population.

Venous-thromboembolism and associated health care utilization in elderly patients with diffuse large B cell lymphoma.

BACKGROUND: Patients with lymphoma have an increased risk of venous thromboembolism (VTE). The authors examined the risk of VTE and subsequent health care utilization in elderly patients with diffuse large B cell lymphoma (DLBCL). METHODS: A total of 5537 DLBCL patients ≥66 years old enrolled in Medicare from the Surveillance, Epidemiology, and End Results registry and a noncancer control group of Medicare beneficiaries (n = 5537) were identified. Cumulative incidence function to examine the risk of VTE 12 months after DLBCL diagnosis was used. Fine and Gray method was used to examine the risk factors associated with VTE risk in multivariable models. Total number of hospitalizations, outpatient visits, and Medicare spending were compared in DLBCL patients with and without VTE. RESULTS: VTE was diagnosed in 8.3% DLBCL patients and 1.5% controls, yielding an 8.6-fold higher risk of VTE in DLBCL in adjusted analysis (95% confidence interval [CI], 6.62-11.20; P < .001). Multivariable regression analysis showed that precancer VTE history was associated with an increased risk of developing VTE after a DLBCL diagnosis (hazard ratio [HR], 5.39; 95% CI, 4.39-6.63), and Asian individuals were associated with a lower risk (HR, 0.54; 95% CI, 0.29-1.00). Patients newly diagnosed with VTE after lymphoma had a 1.7-fold higher rate of hospitalization and a 1.2-fold higher rate of outpatient visits compared to those without, resulting in excess Medicare spending of $22,208 in the first year after DLBCL diagnosis. CONCLUSIONS: Elderly patients with DLBCL have an elevated risk of VTE resulting in excess health care utilization. VTE history before DLBCL was associated with increased risk of post-DLBCL VTE, and Asian individuals were associated with a lower risk of VTE.

Burden of illness and outcomes in second-line large B-cell lymphoma treatment: real-world analysis of Medicare beneficiaries.

Aims: To characterize elderly large B-cell lymphoma patients who progress to second-line treatment to identify potential unmet treatment needs. Patients & methods: Retrospective USA cohort study, patients receiving second-line autologous stem cell transplant (SCT) preparative regimen ('ASCT-intended') versus those who did not; stratified further into those who received a stem cell transplant and those who did not. Primary outcomes were: healthcare resource utilization, costs and adverse events. Results: 1045 patients (22.0%) were included in the ASCT-intended group, 23.3% of whom received SCT (5.1% of entire second-line population). Non-SCT patients were older and had more comorbidities and generally higher rates of healthcare resource utilization and costs. Conclusion: Elderly second-line large B-cell lymphoma patients incurred substantial costs and a minority received potentially curative SCT, suggesting significant unmet need.

Lay abstract Large B-cell lymphoma (LBCL) is an aggressive form of cancer. Although chemotherapy is often initially successful, LBCL recurs in about 50% of patients. For many years, the standard of care for recurrent LBCL has been a course of strong chemotherapy followed by stem cell transplant (SCT). However, many older patients cannot tolerate or do not respond well to chemotherapy and therefore cannot proceed to SCT. In this real-world study of Medicare patients, we found that only 5.1% of patients with recurrent LBCL ever received potentially curative SCT. They also had higher healthcare costs than similar patients who did receive SCT. This shows a significant unmet need in elderly LBCL patients that may potentially be addressed with recent treatment innovations.

The Application of the ThroLy Risk Assessment Model to Predict Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Patients with aggressive lymphomas are at higher risk for venous thromboembolism (VTE). ThroLy is a risk assessment model (RAM) derived to predict the occurrence of VTE in various types of lymphomas. In this study, we assess the clinical application of ThroLy RAM in a unified group of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Hospital databases were searched for patients with DLBCL and radiologically-confirmed VTE. Items in the ThroLy RAM, including prior VTE, reduced mobility, obesity, extranodal disease, mediastinal involvement, neutropenia and hemoglobin < 10.0 g/dL, were retrospectively reviewed. RESULTS: A total of 524 patients, median age 49 (range: 18-90) years were included. Patients had high disease burden; 57.3% with stage III/IV and 34.0% with bulky disease. All were treated on unified guidelines; 63 (12.0%) had primary refractory disease. Venous thromboembolic events were reported in 71 (13.5%) patients. Among 121 patients with high (> 3) ThroLy score, 22.3% developed VTE compared to 8.4% and 12.4% in those with low and intermediate risk scores, respectively (P = .014). Simplifying the ThroLy model into two risk groups; high-risk (score ≥ 3) and low risk (score < 3) can still segregate patients; VTE developed in 44 (17.2%) high-risk patients (n = 256) compared to 27 (10.1%) in the low-risk group (n = 268), P = .038. Neutropenia, a component of the ThroLy, was encountered in only 14 (2.7%) patients. CONCLUSIONS: ThroLy RAM can identify patients with DLBCL at high risk for VTE. Model can be modified by dividing patients into two, rather than three risk groups, and further simplified by omitting neutropenia.

Role of follow-up endoscopic examination in treatment response assessment for patients with gastric diffuse large B cell lymphoma.

OBJECTIVE: According to lymphoma guidelines, gastric diffuse large B cell lymphoma (DLBCL) patients should undergo regular computed tomography (CT) and/or positron emission tomography (PET) examinations to assess treatment response. Endoscopic examinations are not indicated in the guidelines. The aim of this study was to investigate the utility of endoscopic examinations during and after treatment for DLBCL. METHODS: We reviewed the patients diagnosed with gastric DLBCL at Seoul St. Mary's Hospital. All patients underwent endoscopy and radiologic examinations at every follow-up appointment. Radiologic response was defined according to World Health Organization criteria and endoscopic response was determined based on the Groupe d'Etude des Lymphomes de l'Adult grading system that is widely used in post-treatment evaluation of gastric MALT lymphoma. RESULTS: Forty-five patients were analyzed. Within a median follow-up period of 34 months, 35 patients achieved both radiologic and endoscopic complete remission (CR). The median times to endoscopic and radiologic CR were not significantly different (21 versus 16 weeks, p = 0.118). However, in 25 patients with stage I disease, endoscopic CR [median (range), 20 (11-36)] was achieved later than radiologic CR [median (range), 13 (8-36)] (p = 0.027). Among 40 patients who achieved radiologic CR, 35 patients who also achieved endoscopic CR maintained remission during the follow-up. Two of the five patients who achieved radiologic CR without endoscopic CR experienced recurrence. CONCLUSIONS: In gastric DLBCL patients, endoscopic response does not always correlate with radiologic response and might predict disease recurrence. We suggest that follow-up endoscopic examination with biopsy should be performed in addition to radiologic examination.

The significance of pretreatment anemia in the era of R-IPI and NCCN-IPI prognostic risk assessment tools: a dual-center study in diffuse large B-cell lymphoma patients.

BACKGROUND: Anemia is frequently identified at the time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL); however, studies addressing the prognostic significance of this important clinical parameter are lacking. METHODS: In this dual-center study of patients with DLBCL (n = 556) treated with rituximab-containing regimens, we evaluated the prognostic relevance of anemia at diagnosis in a training set (n = 211) and validated our findings in a second independent patient cohort (n = 345). Using Kaplan-Meier curves as well as univariate and multivariate Cox regression models, we analyzed the impact of anemia on 5-year overall survival (OS) and 5-year disease-free survival (DFS) alongside established prognostic indicators including age, tumor stage, the revised International Prognostic Index (R-IPI), and the recently published NCCN-IPI. The influence of anemia on the predictive accuracy of IPI, R-IPI, and NCCN-IPI prognosis scores was subsequently determined using the Harrell's concordance index. RESULTS: Anemia was an independent predictor of impaired OS and DFS at 5 years in both DLBCL patient cohorts (P < 0.001, log-rank test). In multivariate analysis, hemoglobin level was also a strong and independent prognostic indicator in patients stratified according to R-IPI or NCCN-IPI score. In survival analysis, the estimated concordance index, using IPI, R-IPI, and NCCN-IPI stratification measures (0.69, 0.64, and 0.70, respectively), improved to 0.70, 0.68, and 0.73, respectively, when anemia was also considered. CONCLUSION: In this study, we have demonstrated that anemia at the time of diagnosis is an independent predictor of impaired clinical outcome in DLBCL. Furthermore, consideration of hemoglobin levels may improve the accuracy of recently established prognostic tools in lymphoma. Our data encourage further evaluation of the prognostic utility of this readily accessible biological parameter in prospective clinical trials.

Neurolymphomatosis--diagnosis and assessment of treatment response by FDG PET-CT.

Neurolymphomatosis (NL) is lymphomatous infiltration of peripheral nerves, and is an uncommon manifestation of non-Hodgkin's lymphoma (NHL). Although nerve biopsy is the main method for histological diagnosis, a blind nerve biopsy may not be diagnostic. While CT and MRI have been used to detect NL, recent reports demonstrated the benefit of integrated positron emission tomography (PET) using F18-2-fluoro-2-deoxy-D-glucose (FDG) combined with computed tomography (CT). We described the utility of FDG PET-CT in this uncommon subgroup of NHL where it can assist in establishing the diagnosis, the potential to guide sites for biopsy and in the assessment of response to therapy.