Impact of Clinical Trial Design on Recruitment of Racial and Ethnic Minorities.

Knowledge related to how oncology treatment trial design influences enrollment of racial and ethnic minorities is limited. Rigorous identification of clinical trial design parameters that associate favorably with minority accrual provides educational opportunities for individuals interested in designing more representative treatment trials. We identified oncology trials with a minimum of 10 patients at an NCI-Designated Comprehensive Cancer Center from 2010 to 2021. We defined a study endpoint of racial and ethnic minority accrual greater than zero. Multivariable logistic regression was used to determine whether co-variables predicted our study endpoint. P-values of less than 0.05 were considered significant. A total of 352 cancer trials met eligibility criteria. These studies enrolled a total of 7981 patients with a total of 926 racial and ethnic minorities leading to a median enrollment of 10%. Trials open in community sites (yes versus no) were more likely to have a minority patient (OR, 2.21; 95% CI, 1.02-4.96) as well as pilot/phase I studies compared to phase II/III (OR, 3.19; 95% CI, 1.34-8.26). Trials incorporating immunotherapy (yes versus no) were less likely to have a minority patient (OR, 0.47; 95% CI, 0.23-0.94). Trials open in community sites as well as early phase treatment studies were more likely to accrue minority patients. However, studies including immunotherapy were less likely to accrue racial and ethnic minorities. Knowledge gained from our analysis may help individuals design oncology treatment trials that are representative of more diverse populations.

Dual agonist immunostimulatory nanoparticles combine with PD1 blockade for curative neoadjuvant immunotherapy of aggressive cancers.

Lethal cancer is characterized by drug-resistant relapse and metastasis. Here, we evaluate the efficacy of a neoadjuvant therapeutic strategy prior to surgery that combines the immune checkpoint inhibitor anti-PD1 with a powerful immunostimulatory nanoparticle (immuno-NP). Lipid-based immuno-NPs are uniquely designed to co-encapsulate a STING and TLR4 agonist that are functionally synergistic. Efficacy of neoadjuvant combination immunotherapy was assessed in three aggressive murine tumor models, including B16F10 melanoma and 4T1 and D2.A1 breast cancer. Primary splenocytes treated with dual-agonist immuno-NPs produced a 75-fold increased production of interferon ß compared to single-agonist treatments. Systemic delivery facilitated the widespread deposition of immuno-NPs in the perivascular space throughout the tumor mass and their preferential uptake by tumor-resident antigen-presenting cells. Our findings strongly suggested that immuno-NPs, when administered in combination with anti-PD1, harnessed and activated the otherwise "exhausted" CD8+ T cells as key mediators of tumor clearance. Neoadjuvant combination immunotherapy resulted in significant efficacy, curative responses, and protective immunological memory in 71% of good-responding mice bearing B16F10 melanoma tumors and showed similar trends in the two breast cancer models. Finally, this neoadjuvant combination immunotherapy drove the generation of B and T cell de novo epitopes for a comprehensive memory response.

Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia.

Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, has acquired popularity and is used off-label for both auto- and alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data for its use in pediatric blood disorders has been in post-transplant autoimmune cytopenias. Here we describe three patients in whom daratumumab was used outside of post-transplant autoimmune cytopenias, highlighting further potential uses of this medication.