Faculty Bibliography

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35"“3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95"“5.66), P =.054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P =.53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35-3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95-5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

INTRODUCTION/BACKGROUND:Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced cancer. Rheumatoid arthritis (RA) is associated with an increased risk of malignancies; however, patients with RA have been excluded from ICI trials. In this study, we evaluated risk of toxicity after initiation of ICI treatment in RA patients. METHODS:We conducted a single-institution, medical records review analysis to assess the incidence of immune-related adverse events (irAEs) and autoimmune disease (AID) flares among patients with AIDs treated with ICIs from 2011 to 2018. A subgroup analysis for RA patients was performed with frequencies of irAEs and AID flares reported. RESULTS:Twenty-two patients with RA who were treated with ICI for malignancy were identified. At the time of ICI initiation, 86% had inactive RA disease activity. Immune-related adverse events occurred in 7 (32%) of patients, with 2 (9%) developing grade 3 (i.e., severe) irAEs. Immune checkpoint inhibitors were temporarily discontinued because of irAEs in 5 patients (23%), and permanently in 1 patient. Rheumatoid arthritis flares occurred in 12 patients (55%). Of those, 10 (83%) received oral corticosteroids with an adequate treatment response. CONCLUSIONS:Our analysis suggests that irAEs following ICI treatment are not increased among RA patients compared with other cancer patients. Heightened RA disease activity during ICI treatment is common, but most adverse events are manageable with oral corticosteroids, and few require permanent ICI discontinuation. A close collaboration between the oncologist and rheumatologist is advisable when considering ICIs in patients with RA.

Background: The prevalence of autoimmune diseases (AIDs) in patients with lung cancer is approximately 14%. However, patients with pre-existing AIDs have been excluded from trials of immune checkpoint inhibitors (ICIs) known to cause immune activation and lead to immune related adverse events (irAEs) limiting the data on safety and efficacy of these agents. Oncologists are therefore wary to use them in this at-risk population.
Method(s): We conducted a single institution IRB-approved retrospective study to evaluate the safety and efficacy of combination and single agent ICI therapy in patients with pre-existing AIDs and concomitant advanced lung cancer that were treated with ICI from 2011 to 2018. Primary endpoints were incidence of irAEs and AID flares. The secondary endpoint was overall survival (OS).
Result(s): We evaluated records from 29 patients with lung cancer of which 17 (59%) had adenocarcinoma, 10 (34%) had squamous cell carcinoma, two (7%) had small cell cancer, and one (3%) had undifferentiated non-small cell lung cancer. AIDs included rheumatic (72%), gastrointestinal (10%), endocrine (10%) and neurologic (7%). 34% of patients experienced an irAE, though only 7% were severe (grade 3-4 colitis and hepatitis). 66% of patients reported no irAEs at all. The most common irAEs were dermatitis (14%) and colitis (10%). 10% of patients had to permanently discontinue ICIs due to an irAE while 17% temporarily held their ICI. 96% of patients with AIDs were either stable or in remission. AID flares were observed in 28% of patients with 24% requiring treatment. None of the AID flares resulted in permanent discontinuation of ICI therapy. 21% of patients were on immunomodulatory therapies at start of ICI treatment. The use of immunomodulatory medications was not associated with an increased incidence of either irAEs or AID flares. Median OS from ICI initiation was 8.5 months and median PFS was 6 months. There was no statistically significant difference for OS or PFS by presence of irAE or presence of immunomodulatory therapy at start of ICI use.
Conclusion(s): In this cohort, patients with pre-existing AIDs and advanced lung cancer reported fewer AID flares (28%) than has been cited in the literature (approximately 50%). IrAEs were seen at an incidence similar to that observed in patients without AIDs. In our cohort, the majority of adverse reactions were manageable and did not require permanent discontinuation of ICI therapy. Furthermore, the presence of irAEs did not detrimentally affect patients' OS or PFS. Based on these findings, we would consider ICI therapy as an option in select patients with pre-existing autoimmunity. Keywords: toxicity, pre-existing autoimmune disease, Immunotherapy
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OBJECTIVES/OBJECTIVE:Colorectal cancer (CRC) screening continues to be underused, particularly by Latinos. CRC and colonoscopy fear, worry, and fatalism have been identified as screening barriers in Latinos. The study purpose was to examine the relationship of optimism, fatalism, worry, and fear in the context of Latinos referred for CRC screening. METHODS:Our sample included 251 Latinos between the ages of 50 and 83 years who had no personal or immediate family history of CRC, no personal history of gastrointestinal disorder, no colonoscopy in the past 5 years, and received a referral for a colonoscopy. Face-to-face interviews were performed, and data were analyzed using regression models. RESULTS:Greater optimism (β = -1.72, p < 0.000), lower fatalism (β = 0.29, p < 0.01), and absence of family history of cancer (β = 1, p < 0.01) were associated with decreased worry about the colonoscopy. Being female (β = 0.85, p < 0.05) and born in the USA (β = 1.1, p < 0.01) were associated with greater worry about colonoscopy and the possibility of having CRC. Family history of cancer (β = 2.6, p < 0.01), female gender (β = 2.9, p < 0.000), not following the doctor's advice (β = 2.7, p < 0.01), and putting off medical problems (β = 1.9, p < 0.05) were associated with greater fear. In the multiple regression model, lower optimism (β = -0.09, p < 0.05), higher fatalism (β = 0.28, p < 0.01), and female gender (β = 0.9, p < 0.05) were associated with greater worry. CONCLUSIONS:Interventions that address fatalism and promote optimistic beliefs may reduce worry among Latinos referred for colonoscopy. Interventions that alleviate colonoscopy fear because of family history of cancer particularly among Latino women may help improve distress about CRC screening.

PURPOSE/OBJECTIVE:The association between excess body weight and colorectal cancer screening is not well established. The purpose of this analysis was to explore, in the context of patients receiving navigation, whether obesity influences receipt of screening colonoscopy among lower-income Latinos and African Americans. METHODS:This sub-analysis was conducted among Latinos and African American participants who received patient navigation and had complete body mass index (BMI) data (n = 520). Cross-sectional survey data were collected at baseline among individuals 50 years and older who were referred by their primary care providers for a colonoscopy at Mount Sinai's Primary Care Clinic. BMI was based on height and weight data from chart review at baseline, and colonoscopy completion status was collected at 1 year post-baseline. RESULTS:The mean BMI of the sample was 31.17 kg/m(2), with over half (53 %) of the sample categorized as obese. Rates of colonoscopy screening were high (~80 %), regardless of weight status. Adjusting for age, gender, race/ethnicity, family history of colorectal cancer, smoking status, comorbid conditions, income, marital status, insurance, and education, obesity status was not significantly associated with screening behavior among the entire sample (adjusted OR 0.81, CI 0.49-1.32, p = 0.39) or among stratified race/ethnicity and gender groups. CONCLUSIONS:These findings suggest that obesity may not negatively influence receipt of colonoscopy screening in the context of patient navigation among minority participants. Further studies are needed to determine whether this finding will be observed in other populations, with and without the assistance of a patient navigator.