The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes.

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population-based SEER data (2015-2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population-based SEER rates for indolent B-cell (follicular and marginal zone) and T-cell lymphomas, but were 10%-15% higher than SEER rates for aggressive B-cell subtypes (diffuse large B-cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.

Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia.

PURPOSE: Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron). MATERIALS AND METHODS: Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined. RESULTS: Mean anti-SARS-CoV-2 spike immunoglobulin G-binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers (P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/µL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron. CONCLUSION: Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response.

Strategies for Overcoming Disparities for Patients With Hematologic Malignancies and for Improving Enrollment on Clinical Trials.

A multitude of factors contribute to cancer disparities, including, but not limited to, differences in diet, lifestyle, environmental exposures, cultural beliefs, genetic and biological factors related to ancestry, socioeconomic status (SES), and access to health care. More investigation is needed in evaluating these factors in less common cancers and hematological malignancies. Addressing disparities in cancer incidence, prevalence, burden of disease, mortality, and survivorship that have been documented among racial/ethnic minority populations with blood cancers will require multilevel models of the interactions between relevant factors and performance of translational research that uses knowledge of cancer biology to develop and test the feasibility of interventions that can impact human end points. Such work must address a wide range of research areas, including prevention, early detection, diagnosis, treatment, epidemiology, cancer control, treatment, and survivorship. To be effective, efforts should be made to advance these research findings to applications that can transform clinical practice and health care delivery. We reviewed the literature to define a framework for overcoming disparities for patients with hematologic malignancies and to improve patient enrollment on clinical trials.

Priorities for Rural Lymphoma Survivors: A Qualitative Study.

BACKGROUND: We gathered rural patient perspectives on lymphoma care and unmet needs throughout the treatment course to better understand their attitudes toward treatment and their barriers to participating in clinical research studies. PATIENTS AND METHODS: We conducted 12 individual semi-structured telephone interviews in the spring of 2018 with lymphoma survivors from rural counties in Georgia. Patients were identified by a residential address in counties classified as rural according to the Rural-Urban Commuting Areas codes. Participants were recruited from regional patient education conferences and from current research participants at a university research hospital in Georgia. The interviews were recorded and transcribed verbatim. Thematic analysis and MAXQDA, version 18.0.8, were used to facilitate a constant comparative coding process during theme development. RESULTS: The greatest barrier to care was the travel distance. The participants described difficulty navigating between local clinics and larger cancer centers. The lack of communication between the local and specialized clinics complicated the process, and participants had difficulty contacting or seeking advice from the team at the larger cancer centers. Seeking treatment from specialized clinics farther away introduced additional barriers. Most participants agreed that the use of technology was important for improved communication. Participants described lymphoma etiology, subtype-specific studies, alternative therapies, and quality of life as key research priorities. CONCLUSION: These findings suggest that targeted research and interventions are necessary to address the specific needs of rural patients with and survivors of lymphoma. To address the disparity in health outcomes within rural populations, healthcare professionals and investigators can use these data to engage rural patients in treatment decision-making and research planning.

Characterizing Lymphoma Incidence and Disparities for a Cancer Center Catchment Region.

BACKGROUND: Racial disparities in non-Hodgkin lymphoma (NHL) are not well-elucidated for specific catchment areas, which can influence outcomes. Leveraging regional data from a population-based cancer registry may provide unique opportunities to quantify NHL disparities. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results (SEER) data for NHL cases diagnosed in Georgia from 2001 to 2015, we examined NHL incidence rates by lymphoma subtype and racial differences in baseline characteristics and outcomes for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Cox regression models identified predictors of overall survival (OS). RESULTS: SEER documented 38,504 NHL cases in Georgia from 2001 to 2015. The age-adjusted incidence rate for NHL in Georgia increased 1.03% per year, and the annual percentage change was 1.72 in blacks compared with 0.84 in whites. Compared with whites, blacks with DLBCL and FL were more likely to be diagnosed at a younger age (DLBCL, 54.1 vs. 65.5 years; P < .0001; FL, 58.4 vs. 64.0 years; P < .0001) and with B symptoms (DLBCL, 44.4% vs. 33.4%; P < .0001; FL, 28.5% vs. 21.4%; P = .004). Across racial categories, age at diagnosis > 60 years, advanced stage, and B symptoms predicted worse OS in DLBCL and FL. Blacks with DLBCL more commonly were diagnosed with stage III/IV disease (55.5% vs. 48.1%; P < .0001) and had worse 5-year relative survival (58.8% vs. 62.3%; P = .01). CONCLUSIONS: Regional cancer registry data can be used to define incidence patterns and disparities in outcomes across NHL subtypes to help define key targets for interventions in a catchment area.

Maximizing the effectiveness of oral therapies in lymphoid cancers: research gaps and unmet needs.

Oral therapies have become a common treatment choice for several lymphoid cancers. While therapeutic efficacy and patient preference for this therapy type have been reported, there is a lack of knowledge about its effectiveness for lymphoma in clinical practice, particularly in regard to the effects of medication nonadherence. While studies of oral medications in other diseases have shown that adherence is a major factor in outcomes and costs, there is scant research investigating adherence specifically in lymphoma patients, who face unique challenges in their diseases and treatments. To address the limited data available, we constructed a conceptual model and highlighted key opportunities for future research to better elucidate oral therapy adherence in lymphoma. This research will hopefully improve understanding and efficacy of oral treatment for lymphoma patients, while also informing other cancers utilizing oral therapies currently and in the future.

Clinical impact of Internet-based tools to guide therapeutic decisions for mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare cancer with diverse management options. Although clinical practice guidelines have become ubiquitous across medicine, the utility of guidelines for MCL management is limited by provider awareness and the lack of a definitive standard of care. We sought to determine whether expert recommendations, delivered as an online decision support tool, impacted practitioners' therapeutic decisions with MCL. Participants were more likely than the experts to select aggressive regimens for both newly diagnosed and relapsed/refractory MCL. After seeing the expert recommendations, participants revealed that the expert opinion impacted their treatment choices in 103 of 365 clinical scenarios, suggesting that online decision support tools may increase the number of clinicians making treatment decisions for patients with MCL that are concordant with expert consensus recommendations.

Rural and urban patients with diffuse large B-cell and follicular lymphoma experience reduced overall survival: a National Cancer DataBase study.

We examined 83,108 patients with diffuse large B-cell lymphoma (DLBCL) and 43,393 patients with follicular lymphoma (FL) to investigate disparities related to geographic population density, stratified as rural, urban, or metropolitan. We found that urban and rural patients less commonly had private insurance and high socioeconomic status. Urban and rural DLBCL patients were more likely to receive treatment within 14 days of diagnosis (OR 0.93, 95% confidence interval [CI] 0.89-0.98; and OR 0.81, 95% CI 0.72-0.91) while urban FL patients were more likely to have treatment >14 days after diagnosis (OR 1.08, 95% CI 1.01-1.16). Multivariable analyses demonstrated that rural and urban patients had worse overall survival with DLBCL (hazard ratio [HR] 1.09; 95% CI 1-1.19 and HR 1.08; 95% CI 1.04-1.11) and FL (HR 1.11; 95% CI 1.04-1.18 and HR 1.2; 95% CI 1.02-1.41), respectively, suggesting needs for focused study and interventions for these populations.