Real-World Multicenter Study of PD-1 Blockade in HIV-Associated Classical Hodgkin Lymphoma Across the United States.

BACKGROUND: Despite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL). PATIENTS/METHODS: We retrospectively identified patients with HIV-cHL from the "Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)" database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4+ T-cell counts with treatment were measured via Wilcoxon signed-rank tests. Overall response rate (ORR) was defined as the proportion of patients with partial or complete response (PR/CR) per 2014 Lugano classification. RESULTS: We identified 23 patients with HIV-cHL who received a median of 6 cycles of PD-1 blockade: 1 as 1st-line, 6 as 2nd-line, and 16 as ≥3rd-line therapy. Seventeen (74%) patients received monotherapy, 5 (22%) received nivolumab plus brentuximab vedotin, and 1 received nivolumab plus ifosfamide, carboplatin, and etoposide. The median baseline CD4+ T-cell count was 155 cells/µL, which increased to 310 cells/µL at end-of-treatment (P = .009). Three patients had grade 3 imAEs; none required treatment discontinuation. The ORR was 83% with median duration of response of 19.7 months. The median progression-free survival was 21.2 months and did not differ between patients with <200 versus ≥200 CD4+ cells/µL (P = .95). CONCLUSION: Our findings support the use of PD-1 blockade in HIV-cHL for the same indications as the general population with cHL.

Social Determinants of Health and the Link to Colorectal Cancer Outcomes.

OPINION  STATEMENT: Colorectal cancer (CRC) remains the second most deadly cancer in the United States, behind only lung cancer. Despite improvements in incidence due to screening and mortality in part due to better treatments, there are some groups that have not seen these promising changes. American Indian/Alaska Native and non-Hispanic Black individuals, certain geographic regions, and lower socioeconomic groups have all been shown to have worse CRC outcomes. A significant body of evidence has linked these disparities in outcomes to social determinants of health (SDH). SDH are defined by the WHO as "the non-medical factors that influence health outcomes." These factors include but are not limited to income, education, social support, neighborhood of residence, and access to healthcare. Individuals who are negatively impacted by SDH have been shown to have a higher incidence of CRC. These individuals are also less likely to receive adequate CRC screening, are less likely to receive appropriate treatment, and have increased CRC mortality. Interventions that target different SDH domains have been shown to lead to increased rates of CRC screening and receipt of appropriate treatment while simultaneously improving CRC mortality. The aim of this review is to highlight the connection between SDH and CRC outcomes while also exploring interventions that target SDH and thereby improve CRC outcomes.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Age and competing concerns in treatment selection for women with non-metastatic HR+ and HER2- breast cancer: Current clinical practice.

BACKGROUND: Newer adjuvant treatment options for non-metastatic breast cancer have increased survival. There is a need to investigate whether demographic and clinical characteristics of women with hormone receptor-positive, human epidermal growth receptor 2-negative non-metastatic breast cancer (stages I-III) differentially influence treatment decisions in older (age 65 or older) versus younger patients (under age 65). METHODS: In a retrospective electronic medical record review, prevalence ratio with 95% confidence interval for treatment decisions in older vs younger patients was calculated using log binomial regression adjusted for race, stage, and total number of comorbidities. RESULTS: In a sample of 537 patients, 66% were age < 65 and 34% age ≥ 65. Older patients included a higher proportion of White women (85% vs 75%, P = .02), higher number of comorbidities (P ≤0.0001), and lower stage tumors (P = .0004). In multivariable analysis, age ≥ 65 was independently associated with fewer mastectomies (95% CI 0.65-0.96, P = .02), more lumpectomies (95% CI 1.05-1.42, P = .01), and less receipt of radiation treatment (95% CI 0.78-0.97, P = .01) and/or chemotherapy (95% CI 0.73-0.95, P = .006). In multivariate analysis, stage was independently significant for all treatment modalities, except endocrine therapy, and race was not. CONCLUSIONS: This study suggests that age, in addition to breast cancer stage, is a predictor of treatment modality, independent of race and number of comorbidities. Treatment modality reflects a combination of patient preference and clinician assessment of fitness for current standard of care.

Obesity, comorbidities, and treatment selection in Black and White women with early breast cancer.

BACKGROUND: This study investigates obesity and comorbidity in Black and White women with early breast cancer (stages I-III) and their potential impact on treatment decisions for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors. METHODS: In this retrospective chart review, comparisons of frequencies for Black and White patients were calculated with the Fisher exact test. Log binomial regression was used to estimate prevalence ratios (PRs) with 95% confidence intervals for total and individual comorbidities, and multivariable modeling was used to estimate PRs adjusted for age and body mass index (BMI). RESULTS: In a sample of 548 patients, 26% were Black, and 74% were White. Sixty-two percent of Black patients and 32% of White patients were obese (BMI ≥ 30 kg/m2 ; P < .0001). Seventy-five percent of Black patients and 87% of White patients had HR+ tumors (P = .001). Significant intergroup differences were seen for 2 or more total comorbidities (62% of Blacks vs 47% of Whites; P = .001), 2 or more obesity-related comorbidities (33% vs 10%; P < .0001), hypertension (60% vs 32%; P < .0001), diabetes mellitus (23% vs 6%; P < .0001), hypercholesterolemia or hyperlipidemia (28% vs 18%; P = .02), and hypothyroidism (4% vs 11%; P = .012). In women with HR+/HER2- tumors, there were no intergroup differences in treatment decisions regarding the type of surgery, chemotherapy regimen, radiation, or endocrine treatment despite significant differences in the prevalence of obesity and comorbidities. CONCLUSIONS: This study documents significant disparities between Black and White women with early breast cancer with regard to high rates of obesity, overall comorbidities, and obesity-related comorbidities, and it highlights the prevalence of competing risks that may complicate outcomes in breast cancer.

Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model.

The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis. ST266, the biological secretome of Amnion-derived Multipotent Progenitor cells, contains multiple anti-inflammatory cytokines and growth factors. Intranasally administered ST266 accumulated in rodent eyes and optic nerves, attenuated visual dysfunction, and prevented retinal ganglion cell loss in experimental optic neuritis, with reduced inflammation and demyelination. Additionally, ST266 reduced retinal ganglion cell death in vitro. Neuroprotective effects involved oxidative stress reduction, SIRT1-mediated mitochondrial function promotion, and pAKT signaling. Intranasal delivery of neuroprotective ST266 is a potential novel, noninvasive therapeutic modality for the eyes, optic nerves and brain. The unique combination of biologic molecules in ST266 provides an innovative approach with broad implications for suppressing inflammation in autoimmune diseases, and for preventing neuronal damage in acute neuronal injury and chronic neurodegenerative diseases such as multiple sclerosis.