The COVID-19 pandemic exacerbated preexisting barriers to accessing healthcare and social services faced by asylum seekers to the United States. This study aimed to uncover the impact of the first ...year of the COVID-19 pandemic on asylum seekers, including socio-economic stressors and access to medical information, healthcare, and testing.
We conducted 15 semi-structured, in-depth interviews with adult asylum seekers to the U.S. and systematically analyzed the resulting transcripts using a consensual qualitative research approach.
The transcripts yielded six domains: (1) knowledge and understanding of COVID-19; (2) attitudes and practices relating to COVID-19 precautions; (3) experience of COVID-19 symptoms; (4) current physical and mental health; (5) access to and interaction with health care; (6) discrimination based on asylum status.
Although participants had knowledge about COVID-19's communicability and regularly used masks, their living conditions frequently hindered their ability to quarantine and isolate, and their lack of insurance was often a deterrent to them seeking medical care. Notably, immigration status was not a significant factor discouraging participants from seeking care during the pandemic. The findings build on existing knowledge about this community and may help define areas where support and services can be expanded in current and future pandemics.
Objectives
Response to immune checkpoint inhibitor (ICI) remains limited to a subset of patients and predictive biomarkers of response remains an unmet need, limiting our ability to provide precision ...medicine. Using real-world data, we aimed to identify potential clinical prognosticators of ICI response in solid tumor patients.
Methods
We conducted a retrospective analysis of all solid tumor patients treated with ICIs at the Mount Sinai Hospital between January 2011 and April 2017. Predictors assessed included demographics, performance status, co-morbidities, family history of cancer, smoking status, cancer type, metastatic pattern, and type of ICI. Outcomes evaluated include progression free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR). Univariable and multivariable Cox proportional hazard models were constructed to test the association of predictors with outcomes.
Results
We identified 297 ICI-treated patients with diagnosis of non-small cell lung cancer (N = 81, 27.3%), melanoma (N = 73, 24.6%), hepatocellular carcinoma (N = 51, 17.2%), urothelial carcinoma (N = 51, 17.2%), head and neck squamous cell carcinoma (N = 23, 7.7%), and renal cell carcinoma (N = 18, 6.1%). In multivariable analysis, good performance status of ECOG ≤ 2 (PFS, ORR, DCR and OS) and family history of cancer (ORR and DCR) associated with improved ICI response. Bone metastasis was associated with worse outcomes (PFS, ORR, and DCR).
Conclusions
Mechanisms underlying the clinical predictors of response observed in this real-world analysis, such as genetic variants and bone metastasis-tumor microenvironment, warrant further exploration in larger studies incorporating translational endpoints. Consistently positive clinical correlates may help inform patient stratification when considering ICI therapy.
447
Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients with MIBC but ...efforts to advance this paradigm have been complicated by a lack of (a) prospective studies, (b) rigorous approaches to assess and define clinical complete response (cCR), and (c) integration of novel therapies. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance. Patients not achieving cCR were recommended to undergo cystectomy. Coprimary endpoints included (1) cCR rate and (2) association between cCR and 2-year outcomes. The key secondary endpoint was the impact of pre-specified baseline genomic alterations on outcomes. Additional biomarkers to refine patient selection were also explored. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%). Median follow-up is 27 months. 72/76 patients underwent clinical restaging and a cCR was achieved in 33/76 (43%; 95% CI: 32%, 55%). One cCR patient opted for immediate cystectomy (ypTaN0M0). Outcomes are summarized in the Table. Baseline ERCC2, ATM, FANCC, or RB1 alterations were not, but tumor mutational burden ≥ 10 mutations/mb was, significantly associated with the composite endpoint of ypT0 (immediate cystectomy) or 2-year bladder-intact metastasis-free survival (BIMFS). On landmark analysis, VI-RADS (Vesical Imaging–Reporting and Data System) score (3-5 versus 1-2) on restaging MRI (central blinded review) was associated with inferior BIMFS (HR 4.5; p = <0.01) and MFS (HR 19.3; p <0.01). Circulating tumor DNA data will be presented at the meeting. Conclusions: TURBT followed by gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a substantial subset of patients with MIBC. ≥2-year bladder-intact survival is achieved in the majority of patients with a cCR. Clinical trial information: NCT03558087 . Table: see text
Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, ...cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients electing immediate cystectomy. Seventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1), meeting the co-primary objective. The most common adverse events were fatigue, anemia, neutropenia and nausea. Somatic alterations in pre-specified genes (ATM, RB1, FANCC and ERCC2) or increased tumor mutational burden did not improve the positive predictive value of cCR. Exploratory analyses of peripheral blood mass cytometry and soluble protein analytes demonstrated an association between the baseline and on-treatment immune contexture with clinical outcomes. Stringently defined cCR after gemcitabine, cisplatin, plus nivolumab facilitated bladder sparing and warrants further study. ClinicalTrials.gov identifier: NCT03451331 .
Abstract
Disclosure: M. Gogerly-Moragoda: None. U. Sharif Khawaja: None. K.C. Cheesman: None. A. Leiter: None. E.J. Gallagher: Consulting Fee; Self; Novartis Pharmaceuticals, Flare Therapeutics, ...Seagen, SynDevRx.
INTRODUCTION Over the past decade, immune checkpoint inhibitors (ICIs) have transformed cancer therapy in multiple tumor types and improved outcomes. Endocrine immune related adverse events are well recognized side effects of ICIs. ICI induced hypophysitis is potentially life-threatening if not identified and treated. The present study examines the incidence and presentation characteristics of hypophysitis in a real-world cohort including a multitude of ICIs and tumor types. METHODS We conducted a retrospective analysis of all patients treated with ICIs at a large health system from 2011-2020. Patient demographics, type of cancer, type of ICI, endocrine symptoms and laboratory values were collected to characterize hypophysitis within the cohort. RESULTS A total of 1703 patients were treated with ICIs from 2011-2020 of whom 32 (1.9%) developed clinically apparent hypophysitis. Of the 32 patients, 26 patients were confirmed to have secondary adrenal insufficiency (AI), with 6 possible secondary AI. A majority were diagnosed in the outpatient setting (n=21, 66%). For those with hypophysitis, the most common tumor type was melanoma (n=12, 38%), followed by lung cancer (n=9, 28%) and genitourinary cancers (n=8, 25%). Combination cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, ipilimumab and programmed cell death protein 1 (PD-1) inhibitor, nivolumab (n=9, 28%) was the most common regimen, followed by monotherapies ipilimumab (n=6, 19%), nivolumab (n=6, 19%), pembrolizumab (n=6, 19%), the programmed cell death ligand 1 (PD-L1) inhibitor atezolizumab (n=3, 9%), with the remainder on durvalumab or combination durvalumab and tremelimumab. The most common presenting symptom was fatigue (n=21, 66%) with headache (n=8, 25%) and vision changes (n=2, 6%) being less common. The median time to presentation was 5 months with most presenting within 12 months of starting ICI (n=24, 75%). However, a subset of patients presented after 18 months on treatment (n=6, 19%), none of whom received ipilimumab. Seven patients underwent cosyntropin stimulation tests and six had muted responses, despite having low or inappropriately normal ACTH levels. DISCUSSION In this real-world dataset, we found a low percentage of hypophysitis across multiple tumor and ICI types. Secondary AI was most commonly seen with ipilimumab treatment. Notably, the subset of patients who presented after 18 months were all on PD-1 / PD-L1 inhibitors, which potentially indicates a distinct mechanism of hypophysitis with these agents compared with CTLA-4 inhibitors, and the new need to monitor these patients with labs and symptom review beyond the initial few months from ICI start. The muted cortisol response to cosyntropin was surprising in the setting of acute hypophysitis and warrants further investigation in these patients.
Presentation: Thursday, June 15, 2023
Purpose
Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8 + T-cell activity and improves clinical activity of immune ...checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors.
Methods
We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients vs. BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05.
Results
Of 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; 1.54–5.03;
P
= 0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; 0.09, 0.62;
P
= 0.0031).
Conclusions
Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.
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e15097
Background: Improved immunotherapy (IO) outcomes have been observed among non-small cell lung cancer patients with a current or former smoking history. This is thought to be a ...consequence of increased immunogenic mutation burden among smoking-related cancers. We set out to explore the association between smoking status and immunotherapy outcomes in lung and other smoking-associated cancers. Methods: This was a retrospective analysis of 200 consecutive patients with advanced, smoking-associated solid tumor types, treated with single-agent anti-PD1/PDL1 therapy at a single center between July 2014 and February 2018. The primary outcome was overall survival from date of IO initiation. The secondary outcome was overall response, defined as radiographic complete response or partial response, by RECIST 1.1 criteria. The primary predictor was smoking status (former/current smoker vs. never smoker). The primary and secondary outcomes were analyzed using multivariable Cox proportional hazards models and multivariable logistic regression models, respectively. Models were adjusted for age and sex, and stratified by cancer type. Results: The majority of patients were male (64%) with a history of smoking (72%); the average age was 67.1 ± 11.4 years. Cancer types represented were: non-small cell lung cancer (NSCLC, N = 81), hepatocellular carcinoma (HCC, N = 41), urothelial carcinoma (BLCA, N = 39), head and neck squamous cell carcinoma (HNSC, N = 21), and renal cell carcinoma (RCC, N = 18). Over a median follow-up of 11.3 months (range 0.5-53.2), there were 96 deaths and 27% of evaluable patients achieved radiographic response. Response was not evaluable in 27 patients. In multivariable regression analysis, smoking status was not significantly associated with overall survival nor overall response in any cancer type examined (Table). Conclusions: Smoking status was not associated with outcomes in our cohort of IO-treated patients with smoking-associated cancers, though sample size was limited. Table: see text
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e15157
Background: Immune checkpoint inhibitors (ICIs) are widely adopted for multiple indications across various malignancies. Despite the surge in their use, what occurs at ...radiographic progression (rPOD) remains poorly characterized. Herein, we describe patients at our institution that experienced rPOD on ICIs. Methods: We retrospectively reviewed charts of patients (pts) with solid tumors that received at least 2 doses of ICI at our institution from 12/01/2010 to 04/25/2017. Patients’ demographic data, medical history, ICI course, and outcomes were recorded. Characteristics at rPOD included change in tumor size by metastatic site, symptoms, and hospital utilization. Additionally, we characterized outcomes of pts who continued ICIs after rPOD. Fisher’s exact test was performed to identify potential clinical predictors of hospitalization at rPOD. Results: Of the 361 evaluable pts, 238 experienced rPOD. In this cohort, the most common primary sites of disease are: genitourinary (24%), thoracic (24%), skin (21%), and hepatobiliary (15%). At rPOD, 71 (30%) patients were hospitalized within 30 days, with infection (27%) and pain (18%) being the most common reasons. Median survival of pts with hospitalization was 2 months (mos; 95% CI: 0-4), compared to 10 months (95% CI: 8-12) for those not hospitalized (p<0.001). Forty-six (19%) pts continued ICI treatment after rPOD (median duration = 2.8 mos), with eleven (5%) pts continuing for at least 6 months (median duration = 8 mos). Conclusions: In our study of real-world cancer pts treated with ICI, a higher than expected proportion was hospitalized within 30 days after rPOD, and this population had a worse overall survival compared to those that were not. A subgroup of pt with rPOD did not experience clinical progression, and thus treatment was continued, although further benefit was limited to a small subset. Further studies are needed to better understand the underlying mechanism to identify those who benefits from treatment beyond rPOD. Table: see text
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e15109
Background: Regulatory T cells play a key role in protecting kidney cells from ischemic injury. Immune checkpoint inhibitors (ICIs) may increase the risk of acute kidney injury ...via inhibition of regulatory T cells 1, 2. Prospective clinical trials have largely excluded patients with chronic kidney disease (CKD); thus, we have limited knowledge of the safety and efficacy of ICI in these patients. Herein, we hypothesize that patients with CKD receiving ICIs have worse clinical outcomes. Methods: This single-institution retrospective cohort study included adult patients with solid tumors who were treated with ICIs at The Mount Sinai Hospital between 2011 and 2017. Clinical endpoints response to treatment, progression of disease (POD) on treatment, mortality were compared between patients with and without CKD using multivariate logistic regression. Odds ratios were controlled for demographics, primary tumor type, presence of cardiovascular comorbidities, smoking status, incidence of renal adverse events, and a composite of stage of illness with indication for treatment localized—neoadjuvant, localized—adjuvant, regionally advanced, metastatic disease. Data were analyzed using R version 3.5.1 with the following packages: readr, dplyr, broom, lubridate, tableone. Results: 420 patients met inclusion criteria: 399 patients without CKD and 21 patients with CKD. Cohorts are well matched for demographics, smoking status, stage/indication for treatment. The CKD cohort has a higher proportion of patients with urothelial cancer compared to patients without CKD (33% vs 11%) as well as a higher proportion of patients with HTN (81% vs 53%), HF (14% vs 3%), and DM (48% vs 21%). There was no statistical difference in odds of response to treatment OR 0.76, 95% CI 0.26-2.23, POD OR 0.42, 95% CI 0.15-1.17, or mortality OR 2.05, 95% CI 0.71-5.96 between the CKD and non-CKD cohort. Conclusions: The data suggest the presence of CKD is not associated with worse clinical outcomes in cancer patients treated with ICIs. As a small retrospective study, the conclusions are hypothesis-generating but support continued use of immunotherapy in CKD in clinical practice and the inclusion of patients with CKD in immunotherapy clinical trials to further clarify safety and efficacy. Table: see text
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