Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies.

Introduction: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance. Methods: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The primary objective of dose escalation phase Ib was to assess safety, tolerability, and recommended phase II dose. The primary objective of the phase II expansion study was to assess the combination's antitumor activity, including objective response rate and clinical benefit rate. Results: A total of eight patients (five in phase Ib and three in phase II) were evaluable for adverse events (AEs) at our study site. All eight patients experienced at least grade 1 AE. The most common treatment-related AEs were increased serum aspartate aminotransferase (38%), fatigue (38%), anemia (25%), increased alkaline phosphatase (25%), hyperbilirubinemia (25%), hypocalcemia (25%), and hypoalbuminemia (25%). Most of these AEs were grade 1 or 2. None of the patients experienced grade 4 AEs and no drug-related fatal AEs were reported among the eight patients treated in the study. One (13%) patient had stable disease (SD) (captured as unknown by the study sponsor because the evaluation criteria set per protocol was not met) and three (38%) patients had progressive disease. Four (50%) patients developed clinical disease progression based on investigator evaluation. One patient with pancreatic cancer achieved immune-related SD for 26 months while on the study treatments. Conclusion: The study completed phase Ib dose escalation and phase II. However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored.

Digital Health Interventions for Cancer Prevention Among Racial and Ethnic Minority Groups in the United States: A Scoping Review.

OBJECTIVE: The COVID-19 pandemic abruptly accelerated the use of digital health for cancer care. Previously, researchers identified a variety of digital health interventions for cancer prevention. The purpose of the present scoping review was to identify digital health interventions for cancer prevention designed for racial/ethnic minority groups. METHODS: The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and was guided by the Arksey and O'Malley methodological framework. A search of PubMed, Ovid MEDLINE, and CINAHL for peer-reviewed research articles published from database inception to August 21, 2023, was conducted. Peer-reviewed studies published in English that employed digital health interventions for cancer prevention, that were conducted among racial/ethnic minority groups, and that were conducted in the United States were included. Also included were cancer prevention interventions for people who did not have cancer, people who did have cancer, and cancer survivors. Excluded were interventions that included non-Hispanic White individuals, interventions performed outside the United States, interventions that combined face-to-face methods with digital strategies, and interventions that did not clearly include digital health. Articles that focused on technologies for collecting and transmitting health data (e.g., remote patient monitoring) without an explicit tie-in to cancer prevention intervention outcomes were also excluded. RESULTS: Following screening, eight articles met the eligibility criteria. Six of the articles were published prior to the COVID-19 pandemic, and two were published during it. The digital health interventions for cancer prevention in racial/ethnic minority groups included screening (n = 5), emotional support and education (n = 1), human papillomavirus vaccination (n = 1), and education and treatment (n = 1). A consistently measured outcome was intervention efficacy. Four authors explicitly stated that theories or theoretical constructs were employed to guide intervention development. Also, no interventions were created using novel devices such as emerging technologies. CONCLUSIONS: We identified several notable gaps regarding digital health for cancer prevention among racial/ethnic minority groups. Addressing these gaps may help guide continued innovation in the use of digital health for cancer prevention among racial/ethnic minority groups.

A Multivariate Probit Regression of the Uptake of Adolescent Vaccines Among Racial/Ethnic Minority Adolescents Before and During the COVID-19 Pandemic.

PURPOSE: The uptake of adolescent vaccines has improved over the years. However, research of the effects of the COVID-19 pandemic on this uptake among racial/ethnic minority adolescents has been limited. This study was conducted to compare the probability of uptake of the human papillomavirus (HPV); tetanus, diphtheria, and acellular pertussis (Tdap); and quadrivalent meningococcal conjugate (MenACWY) vaccines among racial/ethnic minority adolescents ages 13-17 years in 2019, 2020, and 2021. METHODS: Using a cross-sectional design to examine data from the National Immunization Survey-Teen (2019-2021), multivariate probit regression was used to model variation in uptake of these three adolescent vaccines (n = 38,128). The outcome measures were HPV, Tdap, and MenACWY vaccine uptake. RESULTS: The probability of uptake of HPV vaccine was higher in 2020 (Coef = 0.09 [95% confidence interval (CI), 0.03-0.16]) and 2021 (Coef = 0.07 [95% CI, 0.00-0.15]) than in 2019. The probability of uptake of MenACWY vaccine was higher in 2020 (Coef = 0.08 [95% CI, 0.02-0.15]) than in 2019. The probability of uptake of recommended vaccines varied among racial/ethnic minorities with non-Hispanic Black adolescents exhibiting higher probability of uptake of HPV vaccine (Coef = 0.10 [95% CI, 0.01-0.19]) than Tdap vaccine. U.S. Census region and insurance status were associated with the uptake of all recommended vaccines. DISCUSSION: Progress in the uptake of these recommended vaccines may not have been interrupted by the COVID-19 pandemic. Also, disparities in uptake of the recommended vaccines still exist despite increased uptake during the pandemic. Future research should examine the disparities as well as examine regional differences in the uptake of these three adolescent vaccines.

The prevalence of human papillomavirus vaccination among racial and ethnic minority adolescents during the COVID-19 pandemic.

BACKGROUND: Human papillomavirus (HPV) vaccination among adolescents has steadily improved over the past several years. However, research conducted to determine whether the COVID-19 pandemic disrupted this positive trend in HPV vaccine initiation among racial and ethnic minority adolescents is limited. Therefore, this study was conducted to determine if the COVID-19 pandemic and the resulting changes in the US health-care sector affected the increasing HPV vaccine initiation among non-Hispanic Black and Hispanic adolescents aged 13-17 years. METHODS: Using a cross-sectional design to examine data from the National Immunization Survey-Teen (2019-2021), logistic regression and moderation analysis were used to model race-specific variations in HPV vaccine initiation (n = 49 031). Two-sided P values of up to .05 were considered statistically significant. RESULTS: Hispanic (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.16 to 1.57) and non-Hispanic Black (AOR = 1.29, 95% CI = 1.10 to 1.51) adolescents had higher odds of HPV vaccine initiation than did non-Hispanic White adolescents. Additionally, the odds of HPV vaccine initiation were higher in 2021 (AOR = 1.22, 95% CI = 1.08 to 1.38) than in 2019. Other variables-age, region, sex, insurance status, and poverty status-were also associated with HPV vaccine initiation. CONCLUSION: These findings demonstrate that during the COVID-19 pandemic, racial and ethnic minorities had higher odds of receiving the HPV vaccine. Therefore, more research of the impact of the pandemic on HPV vaccine initiation among non-Hispanic White and racial and ethnic minority adolescents is needed.

Parent-reported provider recommendation of HPV vaccination among minority adolescents before and during the COVID-19 pandemic: Findings from the National Immunization Survey-Teen, 2019-2021.

Provider recommendation of human papillomavirus (HPV) vaccination among adolescents has steadily improved over the years, however, limited research has been conducted to examine if the COVID-19 pandemic disrupted this positive trend in parent-reported provider recommendation among minority adolescents. Therefore, we conducted the present study to determine if there is an association between the pandemic and parent-reported provider recommendation of HPV vaccine among non-Hispanic black and Hispanic adolescents. We also examined whether any changes in parent-reported provider recommendation in the years 2019, 2020, and 2021 differed by race or ethnicity. Using a cross-sectional design to examine data from the National Immunization Survey-Teen (2019-2021), a moderation analysis and logistic regression analysis were performed to model race-specific variation in parent-reported provider recommendation (n = 50,739). We found that Hispanic parents had lower odds (aOR = 0.80 [0.71, 0.91]) of reporting receiving a recommendation compared to non-Hispanic white parents. We also found that the odds of parent-reported provider recommendation were higher in 2020 (aOR = 1.15 [1.03-1.29]) than in 2019. Other variables-age, region, sex, health insurance status, and poverty status-were all associated with parent-reported provider recommendation. These findings demonstrated that the pandemic may not have triggered any race-related gap in the recommendation of HPV vaccines, however, more pandemic-resilient public health efforts are needed to improve parent and provider communication regarding HPV vaccination of adolescents.

Spectrum of Immune Checkpoint Inhibitor Anemias: Results From a Single Center, Early-Phase Clinical Trials Case Series Experience.

Immune checkpoint inhibitor anemias (ICI-A) are a rare entity which can be potentially life-threatening without prompt identification. The goal of the study is to characterize the presentation, evaluation, and outcomes of ICI therapy in early phase clinical trial setting to guide future research and to develop standardized care guidelines. Retrospective chart review of 333 patients who participated in early phase clinical trials at the University of Texas MD Anderson Cancer Center revealed four cases with ICI-A between 2016 and 2020. We identified a spectrum of four cases which included ICI-related autoimmune hemolytic anemias, hemophagocytic lymphohistiocytosis and thrombotic microangiopathy as a result of combinatory investigational therapies involving ICI. Patient presentation, evaluation, bone marrow pathology, interventions, and clinical course were reviewed. The median time to onset of hematological immune-related adverse events (heme-irAEs) in this retrospective series was 3.5 weeks (2 - 6 weeks). One patient had pre-existing untreated chronic lymphocytic leukemia. Glucocorticoids are an effective first-line treatment in most patients although most patients were not rechallenged but successfully had complete recovery and pursued further non-immunotherapy-based therapies. Cognizance of ICI-A in clinical trial setting is paramount to early recognition of heme-irAEs. Further research is needed to identify and stratify risk factors during clinical trial enrollment and optimal management strategies for immune-mediated hematologic toxicities.

Role of Abdominal and Pelvic CT Scans in Diagnosis of Patients with Immunotherapy-Induced Colitis.

Introduction: Colitis is one of the most common immune-related adverse events in patients receiving immune checkpoint inhibitors. Although radiographic changes on computed tomography (CT), such as mild diffuse bowel thickening, mesenteric fat stranding, and mucosal enhancement, have been reported, the utility of CT in diagnosis of patients with suspected immune-related colitis is not well documented. The aim of this retrospective study was to determine the value of CT scans in diagnosis of immunotherapy-induced colitis. Methods: CT scans of the abdomen and pelvis of 34 patients receiving immunotherapy who had a clinical diagnosis of immunotherapy-induced colitis and 19 patients receiving immunotherapy without clinical symptoms of colitis (controls) were evaluated. Segments of the colon (rectum, sigmoid, descending, transverse, ascending, and cecum) were assessed independently by two abdominal imaging specialists, blinded to the clinical diagnosis. Each segment was assessed for radiographic signs such as mucosal enhancement, wall thickening, distension, and periserosal fat stranding. The presence of any of the signs was considered radiographic evidence of colitis. Results: CT findings suggestive of colitis was seen in 20 of 34 patients with symptoms of colitis and in 5 of 19 patients without symptoms of colitis. The sensitivity, specificity, positive predictive value, and negative predictive value for colitis on CT were 58.8%, 73.7%, 80%, and 50%, respectively. Conclusions: We found that CT had a low sensitivity, specificity, and negative predictive value for the diagnosis of immunotherapy-induced colitis. We therefore conclude that CT has a limited role in the diagnosis of patients with suspected uncomplicated immune-related colitis.

Adherence to the Recommended HPV Vaccine Dosing Schedule among Adolescents Aged 13 to 17 Years: Findings from the National Immunization Survey-Teen, 2019-2020.

The 9-valent human papillomavirus (9-vHPV) vaccine uptake rate among adolescents has improved over the years; however, little is known about the adherence to the recommended dosing schedule. This study examines the prevalence and factors associated with adherence to the recommended 9vHPV vaccination dosing schedule among adolescents aged 13 to 17 years. The cross-sectional study was conducted using the 2019-2020 National Immunization Survey-Teen. The parents of 34,619 adolescents were included in our analyses. The overall up-to-date (UTD) prevalence was 57.1%. The UTD prevalence was 60.0% among females and 54.2% among males. Adolescents aged 16 years had the highest UTD prevalence of 63.0%. The UTD prevalence was 61.6% among Hispanics and 54.7% among non-Hispanic Whites. Overall, compared to females, males had 14% lower odds of UTD. The odds of UTD were 1.91 times, 2.08 times, and 1.98 times higher among adolescents aged 15-17 years, respectively, compared to those aged 13 years. Moreover, region, poverty, insurance status, mothers' educational level, and provider recommendation were associated with UTD. Our findings show that adherence to the recommended 9vHPV vaccine schedule is low in the US. Targeted public health efforts are needed to improve the rates of adherence to the recommended 9vHPV dose schedule.