Safety and efficacy of immune checkpoint inhibitor cancer therapy in patients with preexisting type 1 diabetes mellitus.

Introduction: Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM. Methods: This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class. Results: Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy. Discussion: These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.

A community-partnered approach for diversity in COVID-19 vaccine clinical trials.

Introduction: Communities of color have faced disproportionate morbidity and mortality from COVID-19, coupled with historical underrepresentation in US clinical trials, creating challenges for equitable participation in developing and testing a safe and effective COVID-19 vaccine. Methods: To increase diversity, including racial and ethnic representation, in local Los Angeles County NIH-sponsored Phase 3 SARS-CoV-2 vaccine clinical trials, we used deliberative community engagement approaches to form a Community Consultant Panel (CCP) that partnered with trial research teams. Thirteen members were recruited, including expertise from essential workers, community-based and faith-based organizations, or leaders from racial and ethnic minority communities. Results: Working closely with local investigators for the vaccine studies, the CCP provided critical insight on best practices for community trust building, clinical trial participation, and reliable information dissemination regarding COVID-19 vaccines. Modifying recruitment, outreach, and trial protocols led to majority-minority participants (55%-78%) in each of the three vaccine clinical trials. CCP's input led to cultural tailoring of recruitment materials, changes in recruitment messaging, and supportive services to improve trial accessibility and acceptability (transportation, protocols for cultural competency, and support linkages to care in case of an adverse event). Barriers to clinical trial participation unable to be resolved included childcare, requests for after-hours appointment availability, and mobile locations for trial visits. Conclusion: Using deliberative community engagement can provide critical and timely insight into the community-centered barriers to COVID-19 vaccine trial participation, including addressing social determinants of health, trust, clinical trial literacy, structural barriers, and identifying trusted messenger and reliable sources of information.

Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer.

Background and Aims: Colonoscopy is recommended post-acute diverticulitis (AD) to exclude underlying adenocarcinoma (CRC). However, post-AD colonoscopy utility remains controversial. We aimed to examine yield of post-AD colonoscopy in our majority-Hispanic patient population. Methods: Patients undergoing post-AD colonoscopy between 11/1/2015-7/31/2021 were identified from a prospectively maintained endoscopic database. AD cases without computed tomography confirmation were excluded. Pertinent data, including complicated vs uncomplicated AD, fecal immunochemical test (FIT) result post-AD/pre-colonoscopy, and number/type/location of non-advanced adenomas, advanced adenomas, and CRC, were abstracted. Analyses were conducted using two-sample Wilcoxon rank-sum and Fisher's exact tests. Results: 208 patients were included, of whom 62.0% had uncomplicated AD. Median age was 53, 54.3% were female, and 77.4% were Hispanic. Ninety non-advanced adenomas were detected in 45 patients (21.6%), in addition to advanced adenoma in eight patients (3.8%). Two patients (1.0%) had CRC, both of whom had complicated AD in the same location seen on imaging, and one of whom was FIT+ (the other had not undergone FIT). Patients with uncomplicated versus complicated AD had similarly low rates of advanced adenomas (4.7% vs. 2.5%, p=0.713). FIT data were available in 51 patients and positive in three (5.9%); non-advanced adenomas were found in all three FIT+ patients. No FIT- patient had an advanced adenoma or CRC. Conclusion: Colonoscopy post-AD is generally low yield, with CRC being rare and found only in those with complicated AD. Colonoscopy post-complicated AD appears advisable, whereas less invasive testing (e.g. FIT) may be considered post-uncomplicated AD to inform the need for colonoscopy.