Dose Of Immune Checkpoint Inhibitors Research Articles

Outcomes of Budesonide as a Treatment Option for Immune Checkpoint Inhibitor-Related Colitis in Patients with Cancer.

Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC. We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI. Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies. Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.

Sarcoid-like reactions to immune checkpoint inhibitors: Incidence, treatment course, and impact on cancer progression and survival

IntroductionSarcoid-like reactions (SLRs) to immune checkpoint inhibitors (ICIs) are a rare but increasingly recognized immune-related adverse event of which the clinical significance is unclear. MethodsWe conducted a retrospective cohort study at a tertiary academic center of consecutive patients who received at least one dose of ICI from 2013 to 2020. Patient characteristics, risk factors, and outcomes were compared between patients with and without SLR following ICI treatment. ResultsA total of 2963 cancer patients received at least 1 dose of ICI between 2013 and 2020, and 7 patients (0.24 %) developed SLR. There were no significant demographic differences between patients with and without SLR following ICI. SLRs occurred in 5 of 451 (1.07 %) melanoma patients and 2 of 840 (0.24 %) non-small cell lung cancer patients. Two of the 7 patients had multi-organ SLR, and both were symptomatic requiring systemic corticosteroids and permanent ICI discontinuation, while single organ SLR patients did not require immune suppression. Development of SLR did not appear to have negative impact on cancer progression or overall survival; in fact, a trend towards improved progression-free and overall survival was observed (median time: 1363 days vs 127 days, p = 0.091; 1387 days vs 428.5 days, p = 0.19, respectively). ConclusionsSLRs are a known but understudied complication associated with ICI therapy. Multisystem SLR patients were more symptomatic and required ICI discontinuation and immune suppression. Larger studies are needed to fully evaluate the impact of SLR on cancer outcomes.

Two acute kidney injury episodes after ICI therapy: a case report.

A 74-year-old Japanese male with lung squamous cell carcinoma received his first dose of immune checkpoint inhibitors (ICIs): ipilimumab and nivolumab. He developed acute kidney injury (AKI) and was admitted to our department. We diagnosed kidney immune-related adverse effects (irAE), and a kidney biopsy revealed acute tubulointerstitial nephritis. We started oral prednisolone (PSL) and his AKI immediately improved. The patient maintained stable findings after PSL was tapered off. However, seven months after the ICI administration, he developed rapid progressive glomerular nephritis and was admitted to our department again. The second kidney biopsy showed findings consistent with anti-glomerular basement membrane glomerulonephritis. Although the patient was treated with pulse methylprednisolone followed by oral PSL and plasma exchange, he became dependent on maintenance hemodialysis. To our knowledge, no case report has described two different types of biopsy-proven nephritis. In cases of suspected relapsing kidney irAEs, both a relapse of previous nephritis and the development of another type of nephritis should be considered.

Effect of pre-treatment with EGFR-TKIs on immune checkpoint inhibitor-associated interstitial lung disease in lung cancer patients: Analysis using a Japanese claims database.

Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are key drugs for the treatment of EGFR mutation-positive lung cancer. While previous studies reported that the concomitant use of these drugs increases the risk of interstitial lung disease (ILD), the impact of sequential treatment on ILD risk is unknown. This study aimed to analyze the impact of EGFR-TKI pre-treatment on the risk of developing ILD after subsequent ICI administration. We conducted a retrospective study using a Japanese health insurance claims database. ILD-naive lung cancer patients who had first ICI administration during the screening period from July 2014 to February 2019 were selected. Patients who had ILD within 1 year of receiving the first ICI dose were included in the ILD group. Multivariate logistic regression analysis was conducted to evaluate the effect of pre-treatment with EGFR-TKI on the development of ICI-associated ILD. A total of 353 patients were included, of which 61 were included in the ILD group. The median time to onset of ILD after ICI administration was 3 months. Multivariate logistic regression analysis revealed that pre-treatment with EGFR-TKI was not associated with ICI-associated ILD (odds ratio: 0.26, 95% confidence interval: 0.033-2.01). Although further analyses are required to confirm our findings, this study indicated that pre-treatment with EGFR-TKI might not increase the ILD risk after ICI treatment.

Pan-cancer assessment of antineoplastic therapy-induced interstitial lung disease in patients receiving subsequent therapy immediately following immune checkpoint blockade therapy

BackgroundDrug-induced interstitial lung disease (DIILD) is a serious adverse event potentially induced by any antineoplastic agent. Whether cancer patients are predisposed to a higher risk of DIILD after receiving immune checkpoint inhibitors (ICIs) is unknown.MethodsThis study retrospectively assessed the cumulative incidence of DIILD in consecutive cancer patients who received post-ICI antineoplastic treatment within 6 months from the final dose of ICIs. There was also a separate control cohort of 55 ICI-naïve patients with non-small cell lung cancer (NSCLC) who received docetaxel.ResultsOf 552 patients who received ICIs, 186 met the inclusion criteria. The cohort predominantly comprised patients with cancer of the lung, kidney/urinary tract, or gastrointestinal tract. The cumulative incidence of DIILD in the entire cohort at 3 and 6 months was 4.9% (95% confidence interval [CI] 2.4%–8.7%) and 7.2% (95% CI 4.0%–11.5%), respectively. There were significant differences according to cancer type (Gray’s test, P = .04), with the highest cumulative incidence of DIILD in patients with lung cancer being 9.8% (95% CI 4.3%–18.0%) at 3 months and 14.2% (95% CI 7.3%–23.3%) at 6 months. DIILD was caused by docetaxel in six of these 11 lung cancer patients (54.5%). After matching, the cumulative incidence of docetaxel-induced ILD in patients with NSCLC in the post-ICI setting was higher than that in the ICI-naïve setting: 13.0% (95% CI 3.3%–29.7%) vs 4.3% (95% CI 0.3%–18.2%) at 3 months; and 21.7% (95% CI 7.9%–39.9%) vs 4.3% (95% CI 0.3%–18.2%) at 6 months. However, these were not significant differences (hazard ratio, 5.37; 95% CI 0.64–45.33; Fine–Gray P = .12).ConclusionsPatients with lung cancer were at high risk of developing DIILD in subsequent regimens after ICI treatment. Whether NSCLC patients are predisposed to additional risk of docetaxel-induced ILD by prior ICIs warrants further study.

Effectiveness of Immune Checkpoint Inhibitors in Various Tumor Types Treated by Low, Per-Weight, and Conventional Doses at a Tertiary Care Center in Mumbai.

The cost of immune checkpoint inhibitors (ICIs) limits their accessibility to a small number of patients with cancer in low- and middle-income countries. Early-phase clinical trials have shown target inhibition and high activity at doses lower than those registered and evaluated in clinical trials. Here, we report everyday experience of using ICIs in 100 Indian patients, many of whom received lower doses of ICIs. Consecutive patients who received at least one dose of an ICI irrespective of tumor type at a tertiary care hospital in Mumbai, India, that was able to access ICIs for its patients were enrolled. The objectives were to study the doses used over a 3-year time period, and the effectiveness of therapy, assessed primarily by the overall response rate (ORR), overall survival (OS), and progression-free survival were secondary end points. Twenty-five patients were treated with conventional doses of ICIs, 29 patients received lower doses per body weight, and 46 patients received low-dose treatment. The median number of cycles received was 5 (range, 1-28). Seventy-eight patients received ICIs in a palliative setting. The median follow-up time was 10.2, 9.8, and 3.9 months for those receiving fixed approved dosing, per body weight dosing, and low-dose treatment, respectively. There was a trend with time to prescribe lower doses. Response evaluation was available for 92 patients. Twenty-one (five-adjuvant and 16-palliative) patients received ICIs only. The ORR did not differ statistically among different dosing groups, but comparisons are confounded by inclusion of different ICIs, different tumor sites, and concurrent treatments. The median OS was 6.8 (range, 4.6-9.0) months. Adoption of per-body weight and lower dosing of ICIs appears to give acceptable outcomes. Lower dosing can improve access and timely delivery of ICIs in low- and middle-income countries.

Abstract 16450: Increased Monocyte Count and Neutrophil-to-Lymphocyte Ratio With ICI Myocarditis

Introduction: Diagnosing immune checkpoint inhibitor (ICI) myocarditis remains complex in practice, often requiring advanced imaging or invasive endomyocardial biopsy. We constructed an institutional cohort of patients who received at least 1 dose of ICI and developed probable or definite ICI myocarditis. Hypothesis: We hypothesized that routine serum biomarkers, including troponin I, neutrophil-to-lymphocyte ratio (NLR), monocytes, and AST/ALT, would be elevated and peak at diagnosis. Methods: This retrospective cohort study used EHR data from patients on ICI at a single academic institution who developed probable or definite myocarditis from 7/2015 - 1/2023. Inclusion criteria and diagnosis date were defined using Bonaca criteria and/or documented clinical consensus, e.g. initiation of steroids for presumed myocarditis. Primary outcomes were levels of troponin I/high sensitivity troponin I, monocytes, NLR, and AST/ALT. LOESS regression with default smoothing parameter α = 0.75 was used to evaluate biomarker patterns 7 days pre- and post- diagnosis. Results: We included 16 cases of myocarditis. At diagnosis, most patients had at least 1 significant elevation in troponin I (100%), AST (81%), ALT (63%), or monocytes (69%) while on ICI (Figure 1). After diagnosis, absolute monocyte and lymphocyte count initially decreased before rebounding. Serum NLR rose prior to and briefly after diagnosis (Figure 2). Conclusions: Peripheral cardiac and non-cardiac biomarkers change with ICI myocarditis. Further research on routine non-cardiac biomarkers associated with myocarditis and other ICI toxicities may help prevent high-grade adverse events.

Incidence and treatment of checkpoint inhibitor induced immune related adverse events in the emergency department.

438 Background: Immune checkpoint inhibitors (ICPis) are currently indicated for the treatment of various types of cancers. Through inhibition of the cancer cell’s checkpoint mediated T-cell evasion, ICPis allow for sustained T-cell activation and proliferation, resulting in increased cancer cell death. However, due to increased activation and proliferation of cytotoxic T-cells, ICPis have been associated with a wide spectrum of adverse effects, known as immune related adverse effects (irAEs). Although recently updated, the 2018 NCCN and ASCO guidelines state that treatment is based on the location and severity of irAEs. In general, grade 3 toxicities warrant suspension of ICPis and initiation of high-dose corticosteroids. Corticosteroids should then be tapered over the course of at least 4-6 weeks. The diagnosis of an irAE is challenging, toxicities may be misdiagnosed as there is a diverse familiarity with ICPis and their associated irAEs. Subsequently, care may be delayed, and patients may not receive appropriate guideline directed care. Methods: This multi-center chart review included 7 hospitals within a large health system. Our electronic health record was utilized to compile a report of patients who had received ICPIs within 12 months of presentation to an ED within the health system between 9/1/2019 and 9/1/2022. Assessed outcomes included incidence and type of irAE, time between last ICPi dose and presentation to the ED, steroid used for treatment, time to steroid, treatment driver, and the action that deviated from the 2018 ASCO/NCCN guideline directed treatment if applicable. Results: Of the 241 patients receiving an ICPi, 26 (10.8%) experienced an irAE that prompted a visit to an ED within our health system. Guideline directed treatment of irAE(s) was followed 76.9% of the time, with the steroid dose being too low (15.4%) and the steroid taper occurring too quickly (7.7%) being the two reasons for discordant treatment. Treatment started a median of 1.1 after presentation to an ED, with colitis as the most prevalent irAE in 11 patients (42%) presenting. For all patients, there was an average of 20 days between the last ICPi dose and presentation to ED. The main steroid used was methylprednisolone (42%). Conclusions: The 10.8% of patients who experienced an irAE that prompted a visit to an ED within our health system is a lower rate than what has been described in the literature previously, where rates of presentation to an ED due to an irAE ranged from 25-37%. This could be due to previous data coming from before or shortly after the publication of ASCO and NCCN guidelines in 2018, or because our outpatient medical staff has become more aware of irAEs and their appropriate treatment. Limitations include this review was retrospective, no patients had an irAE that was refractory to steroids, and the study period being soon after national guidelines were published.

Association Between Pretreatment Chest Imaging and Immune Checkpoint Inhibitor Pneumonitis Among Patients With Lung Cancer.

Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. A total of 471 patients with lung cancer were included, of which 402 had non-small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69-16.92; P<.001; and HR, 2.81; 95% CI, 1.50-5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17-18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3-5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.

Osimertinib tolerance in a patient with Stevens Johnson syndrome during osimertinib therapy after treatment with pembrolizumab

BackgroundOsimertinib has emerged as an important tool in the treatment of non-small cell lung cancers (NSCLC) with certain activating mutations of epidermal growth factor receptor (EGFR). However, Osimertinib may cause adverse effects, including severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk of certain adverse effects may be increased in the setting of recent use of immune checkpoint inhibitor (ICI) therapy, although it is unclear whether recent use of ICI therapy is a risk factor for Osimertinib-induced SJS specifically.Case presentationWe present a patient with EGFR L858R mutation-positive metastatic NSCLC who developed Osimertinib-induced SJS after recent administration of eight cycles of a pembrolizumab-containing chemotherapy regimen. Osimertinib, which was the best treatment targeting his lung cancer, was avoided due to history of SJS. Four years later, because of unresponsiveness or side effects of alternative treatments, he underwent Osimertinib challenge and tolerated it.ConclusionThis case highlights the importance of multi-disciplinary care and supports the hypothesis that the risk of SJS to Osimertinib is significantly higher in the context of recent administration of ICI therapy and, patients may tolerate Osimertinib after certain time has elapsed after the last dose of ICI.

Pneumonitis after Palliative Thoracic Radiotherapy +/- Immunotherapy: A Retrospective Propensity-Matched Cohort Study

Patients (pts) with advanced lung cancer often receive combined palliative thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICI). There are limited data assessing the toxicities of combined ICI-RT in this setting. We sought to compare the rates of clinically significant pneumonitis among pts with lung cancer receiving palliative thoracic RT with or without recent or concomitant ICI. We hypothesized there would be a higher rate of grade 2+ pneumonitis among RT pts who received recent or concomitant ICI compared to those who did not. We retrospectively identified consecutive pts with advanced/recurrent lung cancer from a tertiary academic center who received palliative thoracic RT with recent (defined as within 95 days of RT start) or concomitant ICI (ICI-RT group) between January 2014 and February 2020. Pts were propensity matched in a 1:1 manner (by age, sex, ECOG, RT modality, and RT dose) to lung cancer pts who received palliative thoracic RT without any history of ICI receipt (RT-only group). The presence and grade (CTCAE v5.0) of pneumonitis were independently assessed by two investigators. The primary endpoint was grade 2+ pneumonitis, estimated using the cumulative incidence function and compared between the ICI-RT and RT-only groups using Gray's test. The secondary endpoint was overall survival, estimated using the Kaplan-Meier method and compared between groups using the log-rank test. A total of 146 pts were included in the study (73 in each group). There were no statistically significant differences between the ICI-RT and RT-only groups with respect to age (median 67.7 vs. 67.6, p = 0.97), sex (52% vs. 52% female, p = 1.00), pre-treatment ECOG 0-1 (74% vs 75%, p = 0.85), or biologically effective dose greater than 45 (48% vs. 48%, p = 1.00). The most common RT regimens were 30 Gy in 10 fractions (33 pts, 23%) and 20 Gy in 5 fractions (18 patients, 12%). A plurality of cases utilized 3DCRT (67 pts, 46%). In the ICI-RT group, the median time from last dose of ICI to the start of palliative RT was 16 days; three pts in this group-initiated ICI while receiving RT treatment. The most common ICI was pembrolizumab (36 pts, 49%). A total of eleven grade 2+ pneumonitis events (nine grade 2 and two grade 3 events) were observed. The ICI-RT group had a higher cumulative incidence of grade 2+ pneumonitis compared with the RT-only group (1-year rate, 12.3% vs. 2.7%, p = 0.029); grade 3 pneumonitis occurred in 1/73 (1.4%) in each group. There was no difference in overall survival between groups (median 239 vs. 218 days, p = 0.76). In pts with advanced lung cancer treated with palliative thoracic RT, recent or concomitant ICI use was associated with a higher cumulative incidence of grade 2+ pneumonitis. However, the incidence of grade 3+ pneumonitis was low (1.4%) regardless of ICI receipt.

Interventional pharmacoeconomics for immune checkpoint inhibitors through alternative dosing strategies.

Immune checkpoint inhibitors (ICIs) are approved for the treatment of a variety of cancer types. The doses of these drugs, though approved by the Food and Drug Administration (FDA), have never been optimised, likely leading to significantly higher doses than required for optimal efficacy. Dose optimisation would hypothetically decrease the risk, severity, and duration of immune-related adverse events, as well as provide an opportunity to reduce costs through interventional pharmacoeconomic strategies such as off-label dose reductions or less frequent dosing. We summarise existing evidence for ICI dose optimisation to advocate for the role of interventional pharmacoeconomics.

Immune checkpoint inhibitor-related adverse events: Real-world experience from a single veterans' affairs medical center.

Immune checkpoint inhibitors (ICIs) are antineoplastic agents associated with a multitude of immune-related adverse events (irAEs). Available data from clinical trials include highly selective patient populations which may limit their applicability to real-world clinical practice. We present a retrospective cohort study of cancer patients treated with ICI therapy at the Zablocki VA Medical Center between 2014 and 2021. Information on demographics, cancer diagnosis, type of therapy, treatment duration, comorbidities, irAE type, and overall survival were collected. We identified 187 patients who received at least one dose of ICI. About half the patients experienced at least one irAE, the most common categories being fatigue, pulmonary, and endocrine irAEs. Approximately half of the irAEs were diagnosed within the first three months of starting ICI therapy, and 60.38% of those who experienced irAEs discontinued ICI therapy. Patients who experienced endocrine or intestinal irAEs had a significantly longer overall survival. Immune-related complications due to ICI therapy are common and can frequently lead to treatment discontinuation in the real-world setting. Endocrine and intestinal irAEs may correlate with improved survival. The ICI-treated patients who received palliative radiation therapy to the bone had less irAEs, possibly due to immunogenic cell death.

Exocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors.

Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01). ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.

Trends of using immune checkpoint inhibitors near end of life in limited resources setting: Experience of single cancer center in the MENA region.

6566 Background: Immune checkpoint inhibitors (ICIs) are standard of care nowadays in the treatment of many solid tumors as single agent or in combination. Recent literature suggested increased use of ICI near end of life; our aim was to find the characteristics of the patients who received ICI 30 days or less before their death. Methods: Data of patients with advanced solid tumors who have (ICI) therapy and died with disease were retrospectively retrieved. Patients were categorized into those dying within 30 days of the last dose of ICI and those receiving the last dose of ICI more than 30 days before death. Variables of potential interest were compared between the two groups by the Chi-square and independent sample t-tests as appropriate. Results: A total of 411 patients were included in this analysis; 135 (33%) received the last dose of ICI within 30 days of death and 276 (67%) received their last dose more than 30 days before death. Major cancer types included: lung (n=214; 52%), kidney (n=61; 15%), melanoma (n=44; 11%), head and neck (n=41; 10%), and others (n=14; 3%). Patients’ characteristics: median age = 58, majority were males (310; 75%), 105 (26%) had ECOG PS ≥3, and 147 (36%) had brain metastasis. Patients who received the last dose of ICI within 30 days of death had more frequent ICU admissions (50 (37%) vs. 60 (22%), p=0.001, and were less likely to die under the care of the hospice care service (22 patients (16%) vs. 84 (31%), p=0.001. In addition, patients who received the last dose of ICI within 30 days of death were more likely to have a full code status (89 (66%) vs. 147 (53%), p=0.015, and have received a lower number of doses of ICI treatments (mean number of doses: 4.2 vs. 6.5 doses, p=0.001). We did not observe any significant difference between the two groups regarding type of cancer, age, gender, ECOG PS, presence of brain metastasis, number of hospital admissions, dying inside hospital, and number of emergency room visits. Conclusions: Immune checkpoint inhibitors may be overused near end of life which leads to minimal clinical benefits, less likelihood of dying under hospice care, and utilization of ICU resources.

Factors associated with myocarditis in patients with cancer treated with immune checkpoint inhibitors.

e14674 Background: Myocarditis is an uncommon but serious adverse event (AE) of immune checkpoint inhibitor (ICI) therapy. We aimed to identify factors associated with ICI-related myocarditis in cancer patients using pooled data from multiple clinical trials. Methods: Data on 25,965 adults receiving at least one dose of an ICI (nivolumab [NIVO] or ipilimumab [IPI])-containing regimen were extracted from corporate safety and clinical trial databases. Patients missing documentation of AEs, indication, or trial ID were excluded. Myocarditis events were identified using MedDRA preferred terms. A nested case-control study design with controls who had no myocarditis selected at random from the risk sets and matched 1:5 on ICI regimen, duration of exposure to ICI regimen, and trial ID was used. Descriptive statistics were used to derive time to onset of myocarditis and to investigate patterns of myositis and rhabdomyolysis relative to myocarditis. A multivariable conditional logistic regression model was used to identify factors associated with myocarditis. Covariates included age, sex, race/ethnicity, medical history (cardiovascular disease, diabetes, sleep apnea), smoking, cancer type, medication use (within the prior 6 months), and co-occurrences of other AEs (pneumonitis, colitis, and hepatitis). Results: Myocarditis was documented in 122/24,106 (0.5%) patients meeting study eligibility criteria. A total of 732 patients (122 cases and 610 matched controls) from 46 trials were included in the analyses. Mean (SD) age was 63 (12) years; 65% of patients were male, 76% Caucasian, and 52% had a history of cardiovascular disease. NIVO + IPI was the most commonly used regimen (36%), followed by NIVO + relatlimab (25%) and NIVO + chemotherapy (14%). Median (Q1-Q3) time to onset of myocarditis was 38 (26-77) days from first dose of ICI. Myositis was reported in 18/122 (15%) cases and in 2/610 (0.3%) controls (p&lt;0.001). Among the 18 cases, a majority (83%) developed myositis within 3 days before the onset of myocarditis. Rhabdomyolysis was reported in 4/122 (3%) cases, all within a month before myocarditis, and in none of the controls (p=0.001). In adjusted analyses, older age (odds ratio 1.38 per 10-year increase, 95% CI 1.12-1.70) and hepatitis (5.69, 2.24-14.44) were significantly associated with the development of myocarditis. Conclusions: In this large cohort of ICI-treated cancer patients, myocarditis had an early onset and was associated with older age and co-occurrences of hepatitis. Due to a low incidence among controls, rhabdomyolysis and myositis could not be included as covariates in adjusted analyses; however bivariate results showed strong associations between myocarditis and rhabdomyolysis or myositis. These findings suggest that co-occurrences of myositis, rhabdomyolysis, or hepatitis are associated with myocarditis and may originate from a more generalized ICI myopathy.

Time to treatment initiation in a retrospective cohort of patients with advanced lung cancer treated with an immune checkpoint inhibitor.

e21199 Background: Advanced lung cancer is diagnosed by imaging through screening, incidental findings, or during the workup of symptoms. Historically, there was no apparent benefit in expediting the times to biopsy, staging, and chemotherapy initiation. However, the widespread first-line use of immune checkpoint inhibitors (ICIs) can introduce delays such as biomarker testing and financial approval. We aimed to test whether the time to ICI treatment initiation was associated with worse clinical outcomes. Methods: We created a retrospective registry of all patients with advanced lung cancer who received at least one dose of an ICI for any first-line indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics and made a validated database. We defined the time to biopsy as the interval between the initial diagnostic imaging of the index cancer and the biopsy. We defined time to treatment initiation (TTI) as the interval between initial imaging and the first dose of ICI. Overall survival was the interval from the biopsy date to death. We used a Cox multivariate regression to model the continuous association of each additional month of TTI with survival. Confidence intervals (CI) were calculated to 95%, and p-values &lt; 0.05 were considered significant. The study had institutional IRB approval. Results: Our cohort consisted of 472 patients diagnosed with advanced lung cancer and treated with first-line ICI. The median time to biopsy was 15.5 days with an interquartile range (IQR) of 5-29 days, median TTI was 51 days (IQR 35-79), and median overall survival was 14.3 months (CI 11.5-16.6). TTI was not associated with survival by unadjusted or multivariate analysis (HR 0.98, CI 0.95-1.01 and HR 1.02, CI 1.00-1.05, respectively). Smoking history (HR 1.011, CI 1.00-1.02 per pack-year) and higher pre-treatment ECOG performance scores (p &lt; 0.01) were associated with worse survival. Tumor histologic subtype, autoimmune comorbidities, and toxic dust exposure were not associated with survival. The time to biopsy was not associated with survival by unadjusted or multivariate analysis (HR 0.97, CI 0.95-1.01, and HR 1.02, CI 0.97-1.07, for each additional week). Among the subset of patients with a symptomatic presentation of cancer (n = 363, 77%), longer TTI was associated with improved survival, but this effect became non-significant in multivariate analysis (HR 0.94, CI 0.89-0.99 and HR 0.96, CI 0.86-1.08, respectively). Conclusions: We did not find evidence that a shorter TTI is associated with improved survival among patients with advanced lung cancer starting first-line ICI. Additional studies are needed to test if baseline disease burden or other clinical factors can identify patients who would benefit from expedited initiation of treatment.

Palliative care consultation and end-of-life outcomes in a retrospective cohort of patients treated with immune checkpoint inhibitors.

6577 Background: Immune checkpoint inhibitors (ICI) can prolong survival for various cancers and are generally available as treatment options for most patients because of their favorable adverse effect profile. Although ICIs provide treatment for many patients who would otherwise be out of options, their variable and often delayed efficacy may postpone the de-escalation of care at the end of life. Palliative Care consultation (PCC) is well-established among patients receiving cytotoxic chemotherapy, but its effectiveness is less certain among patients receiving newer treatment modalities. We aimed to test the association of PCC with end-of-life (EOL) outcomes among patients treated with an ICI for any type of cancer. Methods: We created a retrospective registry of all patients who received at least one dose of ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. The investigators created a secure, cloud-based registry (REDCap), validated it with data quality rules, and resolved all discrepancies; clinical research specialists at Vasta Global captured most of the data. We used the chi-square test to compare categorical variables, defined statistical significance as p &lt; 0.05, and used SAS version 9.4 for analyses. The study had institutional IRB approval. Results: The cohort consisted of 3,142 patients with lung cancer (45%) as the most common cancer type, followed by melanoma (14%) and head and neck squamous cell carcinoma (9%). ICI was most often given in the first line setting (46%) with good baseline performance status (ECOG 0-1, 50%). 915 (29%) patients had PCC, which was associated with a higher rate of code status de-escalation from “Full Code” at any point before death (92% vs. 87%, p 0.007). There was no association between PCC and either the initiation of ICI within 30 days of death (7% vs. 5%, p .0172) or any dose of ICI within 14 days of death (5% vs. 6%, p 0.33). Among patients with a confirmed location of death (1013, 32%), PCC was associated with a similar rate of death in the hospital at any level of care (30% vs. 28%, p 0.51). Conclusions: PCC was associated with code status de-escalation before death but similar risks of late ICI dosing or inpatient status at the time of death. Further studies are needed to risk-stratify patients starting ICI to identify the subgroups that would benefit the most from PCC.

Safety of checkpoint inhibitors in older patients with genitourinary cancers.

12059 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients with genitourinary (GU) cancers however many of the clinical trials that have led to the approval of ICIs in GU cancers often have low enrollments of older patients aged 65 and above for which safety data in this cohort is limited. Methods: A retrospective study was performed that included all patients aged 65 and older with kidney, bladder, and upper tract urothelial carcinoma (UTUC), who were treated at the University of Florida Health Cancer Center between January 2018 and September 2022, and received at least one dose of ICI (pembrolizumab, nivolumab, ipilimumab with nivolumab, avelumab, or atezolizumab). Data was collected on all documented immune related adverse events (irAEs) that were deemed attributable to the checkpoint inhibitor by the treating provider. The grading of toxicities was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: We identified a total of 139 patients who met the inclusion criteria of our study. The ages of patients ranged from 65 to 93 and the median age was 74. Females accounted for 31 patients (22%) while 108 patients (78%) were male. There were 56 patients (40%) with bladder cancer, 58 patients (42%) with kidney cancer, and 25 patients (18%) with UTUC. An irAE was documented in 76 patients (55%) while 63 patients (45%) had no documented irAE. Patients were categorized by the highest grade of toxicity experienced. A Grade 1 toxicity was found in 15 patients (11%), while a grade 2 toxicity was found in 41 patients (29%), with 18 patients (13%) having a grade 3 toxicity, and 2 patients (1%) experiencing a grade 4 toxicity. There were no documented grade 5 toxicities, i.e. no deaths were directly attributed to treatment. We found that 27 patients (19%) required either oral or intravenous steroids to manage their irAE. Discontinuation of treatment due to an irAE was observed in 16 patients (12%). Inpatient hospitalization due to an irAE occurred in 12 patients (9%). Conclusions: Our study demonstrates that the majority of patients aged 65 and older either have no irAEs or developed mild irAEs when treated with ICIs. Severe and life-threatening adverse events are uncommon, rarely require hospital admission, and did not lead to any deaths. This study should help to provide valuable information on the safety of checkpoint inhibitors in older patients with GU cancers and assist in the shared decision-making process for cancer treatment. [Table: see text]

Clinical outcomes in patients with metastatic non-small cell lung cancer and head and neck squamous cell cancer treated with immune checkpoint inhibitors according to COVID-19 vaccination status.

e14696 Background: Immune checkpoint inhibitor (ICI) constitute the mainstay of therapy in metastatic non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC). Infectious vaccines administered intratumorally or systemically have been suggested to enhance response to ICI and improve outcomes. No data is available on the effect of COVID-19 vaccines on clinical outcomes in patients treated with ICI. The aim of the study is to investigate overall survival (OS), progression-free survival (PFS), and immune related adverse events (IRAEs) according to mRNA COVID-19 vaccination status in patients with metastatic NSCLC and HNSCC who were treated with ICI. Methods: We performed retrospective analysis of clinical outcomes between a cohort of patients treated with ICI who received at least one dose of COVID-19 vaccine, and a historic control group of patients who did not receive COVID-19 vaccine and did not have documented COVID-19 infection. We included patients with metastatic NSCLC and HNSCC who had received at least one dose of ICI, either as monotherapy or in combination with chemotherapy or targeted therapy. Patients were stratified by age, gender, ethnicity, COVID-19 vaccination status, number of vaccinations, treatment type (monotherapy versus combined), treatment line, and PD-L1 status. Endpoints included IRAEs, PFS and OS. Results: A total of 151 patients met inclusion criteria (94 vaccinated and 57 control). Mean age at diagnosis was 62 years, the majority were female (51%), African American (58.3%), and received ICI monotherapy (57.6%). There was prolonged OS in patients who received COVID-19 vaccination versus control group ( p-value=0.04). In a multivariate analysis, patients in the COVID-19 vaccine arm had significantly reduced hazard of dying (HR:0.49, p =0.0446) when controlled for all of the above variables, and each additional received vaccine was associated with significant reduced hazard (HR=0.701, p-value = 0.0099). Race and type of cancer were statistically associated with PFS. Controlled for these factors, COVID arm patients had reduced hazard of disease progression (HR = 0.58, p-value = 0.0506), and each additional received mRNA vaccine was associated with a significantly reduced hazard of progression (HR = 0.74, p-value = 0.0046). There was no significant difference in the rate of IRAEs between vaccinated and non-vaccinated patients ( p=0.71). Conclusions: In this sample of patients with metastatic NSCLC and HNSCC who received ICI, there was significant improvement in OS between patients who received a COVID-19 vaccine compared patients who did not receive vaccination and did not have COVID-19 infection. There were no significant differences in IRAEs. Further studies are required to assess whether there is a synergistic effect between COVID-19 vaccination and ICI efficacy.