Racial and Ethnic Variation in Receipt and Intensity of Active Surveillance for Older Patients With Localized Prostate Cancer.

INTRODUCTION: The use of active surveillance (AS) for prostate cancer is increasing, and racial disparities have been identified in its implementation. We investigated differences by race and ethnicity in the utilization and intensity of AS by race and ethnicity among older men with low- and favorable intermediate-risk prostate cancer, with particular focus on the integration of multiparametric MRI (mpMRI) into AS protocols. METHODS: Using the Surveillance, Epidemiology, and End Results and Medicare fee-for-service linked database, we identified a cohort of men diagnosed between 2010 and 2017 with low- or favorable intermediate-risk prostate cancer. The odds of receiving AS were compared by patient race and ethnicity using multivariable logistic regression models, while the rates of usage of PSA tests, biopsy, and mpMRI within 2 years of diagnosis among men on AS were assessed using multivariable Poisson regression models. RESULTS: Our cohort included 33,542 men. The proportion of men with low-risk disease who underwent AS increased from 29.5% in 2010 to 51.7% in 2017, while the proportion among men with favorable intermediate disease grew from 11.4% to 17.2%. Hispanic (odds ratio [OR] = 0.68, 95% CI 0.58-0.79) and non-Hispanic Black men (OR = 0.78, 95% CI 0.68-0.89) were less likely to receive AS than non-Hispanic White men for low-risk disease, while non-Hispanic Black men were more likely to receive AS for favorable intermediate disease (OR = 1.21, 95% CI 1.04-1.39). Non-Hispanic Black men receiving AS underwent prostate MRI at a lower rate compared to non-Hispanic White men, regardless of whether they had low-risk (incidence rate ratio = 0.77, 95% CI 0.61-0.97) or favorable intermediate-risk (incidence rate ratio = 0.61, 95% CI 0.44-0.83) disease, respectively. CONCLUSIONS: The overall adoption of AS for low-risk prostate cancer increased among Medicare fee-for-service beneficiaries. However, a significant disparity exists for non-Hispanic Black men, as they exhibit lower rates of AS utilization. Moreover, non-Hispanic Black men are less likely to have access to novel technologies, such as mpMRI, as part of their AS protocols.

Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study.

The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies. The overall response rate (ORR) in our cohort was 62%, with a ≥ very good partial remission (VGPR) rate of 51%. The ORR in patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively (p = 0.23). At a median follow-up of 3.5 months (range, 0.39-10.92), the estimated 3 month and 6 month progression free survival (PFS) was 57% (95% CI, 48%, 68%) and 52% (95% CI, 42%, 64%) respectively. The incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11% respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients respectively. 78 unique infections were diagnosed in 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% vs 26% respectively. Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (Hazard ratio [HR] 0.33; 95% CI 0.17, 0.64; p = 0.001).

Adipocyte-Secreted IL-6 Sensitizes Macrophages to IL-4 Signaling.

Complex bidirectional cross talk between adipocytes and adipose tissue immune cells plays an important role in regulating adipose function, inflammation, and insulin responsiveness. Adipocytes secrete the pleiotropic cytokine IL-6 in response to both inflammatory and catabolic stimuli. Previous studies have suggested that IL-6 secretion from adipocytes in obesity may promote adipose tissue inflammation. Here, we investigated catabolic stimulation of adipocyte IL-6 secretion and its impact on adipose tissue immune cells. In obesity, catecholamine resistance reduces cAMP-driven adipocyte IL-6 secretion in response to catabolic signals. By restoring adipocyte catecholamine sensitivity in obese adipocytes, amlexanox stimulates adipocyte-specific IL-6 secretion. We report that in this context, adipocyte-secreted IL-6 activates local macrophage STAT3 to promote Il4ra expression, thereby sensitizing them to IL-4 signaling and promoting an anti-inflammatory gene expression pattern. Supporting a paracrine adipocyte to macrophage mechanism, these effects could be recapitulated using adipocyte conditioned media to pretreat bone marrow-derived macrophages prior to polarization with IL-4. The effects of IL-6 signaling in adipose tissue are complex and context specific. These results suggest that cAMP-driven IL-6 secretion from adipocytes sensitizes adipose tissue macrophages to IL-4 signaling.

Evaluating the impact of eligibility criteria in first-line clinical trials for follicular lymphoma: a MER/LEO cohort analysis.

Cancer clinical trial eligibility criteria may create patient populations studied in trials that do not reflect the patient populations treated in the real-world setting. Follicular lymphoma (FL) is an indolent lymphoma with heterogeneous presentations across a broad range of individuals, resulting in many acceptable management strategies. We evaluated how first-line clinical trial eligibility criteria impacted the demographic makeup and outcomes of patients with FL for whom systemic therapy might be considered. We compared the characteristics of 196 patients with FL from a single institution to eligibility criteria from 10 first-line FL trials on clinicaltrials.gov. Next, we tabulated eligibility criteria from 24 first-line FL protocols and evaluated their impact on 1198 patients with FL with stages II to IV disease from the prospective Molecular Epidemiology Resource (MER) and Lymphoma Epidemiology of Outcomes (LEO) cohort studies. We found that 39.8% and 52.7% of patients with FL might be excluded from clinical trials based on eligibility criteria derived from clinicaltrials.gov and protocol documents, respectively. Patients excluded because of renal function, prior malignancy, and self-reported serious health conditions tended to be older. Expanding stage requirement from III-IV to II-IV, and platelet requirement from ≥150 000 to ≥75 000 increased population size by 21% and 8%, respectively, in MER and by 16% and 13%, respectively, in LEO, without impacting patient demographics or outcomes. These data suggest that management of older individuals with FL may not be fully informed by recent clinical trials. Moreover, liberalizing stage and platelet criteria might expand the eligible population and allow for quicker trial accrual without impacting outcomes.

Age Differences in Clinical Trial Understanding in Non-Hodgkin Lymphoma Patients.

BACKGROUND: Clinical trials are often an important component of cancer care but are misunderstood by many patients. Few studies have examined age differences in clinical trial understanding in older versus younger adults, especially among patients with indolent non-Hodgkin lymphoma (NHL), a slowly progressive and not typically curable cancer diagnosed primarily in older adults. PATIENTS AND METHODS: Participants aged ≥21 years with a diagnosis of NHL were recruited from a single academic medical center in an urban setting. Age was dichotomized as <65 and ≥65 years. Clinical trial understanding was assessed using a four-item survey of potential goals of a clinical trial, with responses including "yes," "no," and "I don't know." Survey responses were examined by age using Chi-square tests. RESULTS: The sample was comprised of 74 patients who were predominantly non-Latino White, with a mean age of 60.4 years (SD = 12.27). Compared to younger patients, older patients were more likely to respond "I don't know" to the clinical trial goals of reducing the lymphoma (41.4% vs. 13.3%; P = .023) and keeping the lymphoma from worsening (41.4% vs. 13.3%; P = .017). Age differences for the remaining goals were not statistically significant. Similar findings emerged when the sample was restricted to patients under active surveillance. CONCLUSION: Relative to younger adults, older adults may have a less nuanced understanding of clinical trial goals. Therefore, older adults may benefit from developmentally-tailored interventions to improve clinical trial understanding. Future research should examine the relationship between clinical trial understanding and enrollment by age using validated measures in diverse samples.

An Assessment of Race as a Risk Factor for Doxorubicin-Related Cardiotoxicity in Diffuse Large B-Cell Lymphoma.

BACKGROUND: Doxorubicin carries a risk of congestive heart failure (CHF). Black race has been suggested as a risk factor for doxorubicin-related cardiotoxicity, but data are limited. We assessed whether HF occurs at higher rates in Black patients compared to White patients who receive doxorubicin for DLBCL, and evaluated race as an independent risk factor for the development of HF after adjusting for known risk factors. PATIENTS AND METHODS: We used SEER-Medicare to identify patients 66 years and older with DLBCL. We excluded patients with CHF documented prior to diagnosis with DLBCL. We assessed for hypertension, type 2 diabetes, coronary artery disease, and arrhythmias prior to diagnosis with DLBCL. The primary outcome was documented CHF at any point following DLBCL diagnosis. Secondary outcomes included CHF in the first year following diagnosis and death. We performed analyses additionally stratified by cumulative dose of doxorubicin. RESULTS: Our study population consisted of 8,604 patients (White 96.8%, Black 3.2%). In both Kaplan-Meier and competing risk analyses, we observed no significant difference in the incidence of CHF between Black and White patients, both before and after adjusting for covariates. Finally, we observed no significant differences in the incidence of CHF by race after stratification by cumulative doxorubicin dose. CONCLUSIONS: CHF is common following doxorubicin chemotherapy for DLBCL in older patients. No association was observed between Black race and the onset of heart failure in this setting. Rigorous screening for known clinical risk factors is likely more relevant than race in treatment selection and optimization.

Evaluation of the prognostic utility of bone marrow biopsy in diffuse large B-Cell lymphoma in the SEER-Medicare dataset.

Positron emission tomography-computed tomography (PET-CT) has become the primary modality for staging in diffuse large B-cell lymphoma (DLBCL), whereas the role of staging bone marrow biopsy (BMB) has become less clear. In this analysis, we included 7,005 DLBCL patients in SEER-Medicare who received either PET-CT without BMB (PET-CT w/o BMB), CT with BMB (CT w/ BMB), or both PET-CT and BMB (PET-CT w/ BMB). The proportion of patients undergoing PET-CT increased across years of diagnosis, while the proportion undergoing CT or BMB decreased. In a fully adjusted Cox proportional hazards model, PET-CT w/ BMB was associated with a marginally superior OS compared to PET-CT w/o BMB. Notably, the association between PET-CT w/ BMB and OS was strongest in patients ≤70 years, but was not present when looking at individual stage of diagnosis. Overall, these data do not provide sufficient support to eliminate staging BMB in patients who undergo PET-CT.

Macrophage Proliferation Sustains Adipose Tissue Inflammation in Formerly Obese Mice.

Obesity causes dramatic proinflammatory changes in the adipose tissue immune environment, but relatively little is known regarding how this inflammation responds to weight loss (WL). To understand the mechanisms by which meta-inflammation resolves during WL, we examined adipose tissue leukocytes in mice after withdrawal of a high-fat diet. After 8 weeks of WL, mice achieved similar weights and glucose tolerance values as age-matched lean controls but showed abnormal insulin tolerance. Despite fat mass normalization, total and CD11c+ adipose tissue macrophage (ATM) content remained elevated in WL mice for up to 6 months and was associated with persistent fibrosis in adipose tissue. ATMs in formerly obese mice demonstrated a proinflammatory profile, including elevated expression of interferon-γ, tumor necrosis factor-α, and interleukin-1ß. T-cell-deficient Rag1-/- mice showed a degree of ATM persistence similar to that in WT mice, but with reduced inflammatory gene expression. ATM proliferation was identified as the predominant mechanism by which ATMs are retained in adipose tissue with WL. Our study suggests that WL does not completely resolve obesity-induced ATM activation, which may contribute to the persistent adipose tissue damage and reduced insulin sensitivity observed in formerly obese mice.