e14651 Background: CheckMate-067 recently trial demonstrated the significant long-term survival benefit of combining ipilimumab and nivolumab versus single-agent immune checkpoint inhibitors (ICIs) in advanced-stage melanoma. While this approach has improved outcomes, melanoma treatment is associated with a high incidence of immune-related adverse events (irAEs), which may be further amplified with dual ICI therapy. Despite this, the development and patterns of multiple irAEs remain poorly understood. This study aimed to elucidate the characteristics and progression of irAEs, with a particular focus on the occurrence of multiple events. Methods: We created an IRB-approved retrospective registry of all melanoma patients who received at least one dose of an ICI between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and outreach clinics. Treatment-emergent adverse events documented in the electronic medical record were reviewed, with attribution and severity estimated using the Common Terminology Criteria for Adverse Events. Case report forms were stored in REDCap and validated with data quality rules. Categorical variables were compared using Chi-squared or Fisher’s exact tests as appropriate, with significance defined as p < 0.05. Results: The cohort comprised 443 patients with a mean age of 63.1 years (SD 13.4). The majority were white (95.9%) and male (67.5%). Most common ICI used were single-agent nivolumab (n = 176, 39.7%), pembrolizumab (n = 110, 24.8%), and ipilimumab (n = 60, 13.5%) while 45 (10%) received nivolumab with ipilimumab. Remaining patients received other combinations. In total, 233 (59.6%) experienced at least irAE. Ipilimumab had the lowest irAE incidence (46.7%) while ipilimumab + nivolumab the highest (80%). Common irAE included dermatitis (n = 75, 16.9%), colitis (n = 61, 13.8%), and thyroid dysfunction (n = 38, 8.6%). Ipilimumab + pembrolizumab showed the highest incidence of dermatitis (n = 7, 31.8%; p = 0.06), while ipilimumab + nivolumab the highest rate of colitis (n = 16, 35.6%; p < 0.01) and thyroid dysfunction (n = 7, 15.6%; p = 0.08). Overall, 141 patients (36.1%) experienced one irAE, 66 (16.88%) had two, 16 (4.09%) experienced three, and 10 (2.56%) were affected by four or more. Incidence of multiple irAE was significantly heterogenous among ICI agents with nivolumab + ipilimumab having highest rates for 1, 2, and > = 4 (16 (35.6%, 16 (35.6%); overall p < 0.01. Conclusions: ICI treatment for melanoma is associated with a heterogeneous risk profile for both individual and multiple irAE. Among the agents studied, the combination of ipilimumab and nivolumab exhibited the highest incidence of irAE affecting different organ systems, as well as the highest rate of multiple irAE. These findings align with the previously demonstrated survival benefits among patients with irAE, reinforcing the potential relationship between irAEs and treatment efficacy. Future translational study into underlying mechanism, especially in the distinct multiple irAE population may be warranted.

Disclosure: B. Safa: None. J. Oakes: None. J.D. Simmons: None. H. Nian: None. L.A. Kirk: None. E. Olson: None. M. Gonzales: None. R.D. Gangula: None. A.C. Cassidy: None. L. Zhu: None. A. Matta: None. S. Bailin: None. C.L. Gabriel: None. C.N. Wanjalla: None. M. Luther: None. J.R. Koethe: None. S.A. Kalams: None. M. Mashayekhi: None. Monocyte-platelet aggregates (MPAs) are increasingly recognized as contributors to inflammation and thrombosis, and are increased in obesity. These aggregates increase inflammation through cytokine and chemokine secretion, contributing to vascular inflammation and the recruitment of leukocytes, linking immune dysregulation to cardiometabolic diseases. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have beneficial effects on cardiometabolic diseases, though the mechanisms are not fully understood. This study tests the hypothesis that the SGLT2 inhibitor empagliflozin reduces inflammation by modulating monocyte-platelet aggregates (MPAs), which is a potential mechanism for the observed cardiometabolic benefits. This pilot study involved eight women with obesity and pre-diabetes as defined by the ADA criteria. Baseline characteristics included mean age of 61±6.1 years, weight of 93±16.9 kg, and BMI of 35.6±4 kg/m2. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, after 2 and 12 weeks of treatment with empagliflozin (25mg/day). Single-cell RNA sequencing was performed to identify and characterize immune cell populations. We used the SCENITH protocol (Single Cell ENergetic metabolism by profilIng Translation inHibition) to define the metabolic profile of MPAs using PBMCs from healthy controls. Metabolic difference was tested using paired t-test. Empagliflozin significantly reduced MPAs at 2 weeks (-2.88% ± 2.11, p = 0.018) and 12 weeks (-4.06% ± 2.11, p = 0.002). Pathway enrichment analysis of differentially expressed genes in MPAs revealed heightened signatures of metabolic activity compared to classical monocytes. Metabolic activity using the SCENITH protocol revealed increased fatty acid oxidation capacity in MPAs compared to classical monocytes (3.92% ±1.67, p= 0.002). This study provides the first human evidence that empagliflozin reduces MPAs, mediators of inflammation and thrombosis. We further demonstrate that MPAs have heightened fatty acid oxidation capacity. The ability of empagliflozin to reduce MPAs and modulate their metabolic activity is a mechanism that may contribute to its cardiometabolic benefits. A randomized controlled trial to explore the broader mechanistic effects of empagliflozin on immune function and metabolism is ongoing. Presentation: Sunday, July 13, 2025

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are diabetes drugs that reduce cardiometabolic diseases in patients with and without diabetes through unclear mechanisms. SGLT2is also reduce inflammation in animals and in vitro. We hypothesized that SGLT2is reduce inflammation in humans as a mechanism of cardiometabolic benefit. In a pilot, we treated eight women with obesity and pre-diabetes with the SGLT2i empagliflozin (25 mg/day) and collected subcutaneous adipose and blood at baseline, 2 and 12 weeks of treatment. We performed single-cell RNA sequencing and computational metabolic modeling on immune cells. Baseline characteristics include age 61±6.1yrs, weight 93±16.9kg, and BMI 35.6±4kg/m². Empagliflozin upregulated genes involved in mitochondrial metabolism and glutathione synthesis, important in the oxidative stress response, in lipid-associated macrophages (LAMs; p < 0.001). We also found that empagliflozin reduced monocyte-platelet aggregates (MPAs) in blood (-2.9±2.1% [-5.0, -0.8], p = 0.018 at 2 weeks; -4.1±2.1 [-6.2, -1.9], p = 0.002] at 12 weeks). MPAs are key mediators of vascular inflammation in cardiovascular disease. In summary, we found that empagliflozin increases expression of genes associated with mitochondrial metabolism and oxidative stress in adipose LAMs and decreases circulating MPAs. These changes may contribute to the cardiometabolic benefits seen with these drugs. Future studies will validate above findings in an ongoing randomized trial. Immune Mechanisms of Human Disease (HUM)

BACKGROUND:Nearly half of patients with cancer are diagnosed at 70 years or older, which presents challenges in cancer care due to their high comorbidity burden and the underrepresentation of this age group in clinical trials. This retrospective study evaluated the association between comorbidity burden and immune checkpoint inhibitors (ICIs) treatment outcomes among older adults. METHODS:Data were collected from patients aged 70 years or older at the time of diagnosis who were treated with ICIs from 2011 to 2022. Key clinical outcomes include changes in performance status, overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs) and were compared between low baseline Charlson Comorbidity Index (CCI) and high CCI (<4 vs. ≥4) groups. RESULTS:Among 1,223 patients, patients with CCI scores ≥4 (n = 300) had a significantly shorter OS (11.4 vs. 13.6 months, p = 0.0461) but similar PFS (8.0 vs. 7.7 months, p = 0.258) compared to patients with CCI scores <4. There was no significant difference in changes in performance status pre- and post-treatment (p = 0.14) or in the irAE prevalence between the two groups (39.3% vs. 38.3%, p = 0.786). CONCLUSION:Our study suggests that ICIs are safe in patients with high comorbidity burden but that the presence of pre-treatment comorbidities decreases overall survival.

12082 Background: Immune checkpoint inhibitors (ICIs) have been shown to be effective against a wide range of cancers and are available to most patients due to their favorable side effect profile. Studies have shown that palliative care consultation prolongs overall survival (OS) in patients with advanced cancer, but most of these studies assessed cytotoxic chemotherapy and not ICIs. Other studies have shown that outpatient palliative care consultation (OPCC) has a greater effect on a variety of end-of-life outcomes than in the inpatient setting. Our study aims to analyze the association between OPCC and survival in patients with lung cancer treated with an ICI. Methods: We designed a retrospective registry of all patients at a comprehensive cancer center and its outreach clinics who received one or more doses of an ICI. The investigators created a secure, cloud-based registry (REDCap), validated it with data quality rules, resolved all discrepancies, and obtained data on palliative care encounters; clinical research specialists at Vasta Global (New York, NY) captured most of the data. Comparisons were made using chi-square or Fisher’s exact for categorical variables. Cox proportional hazards model was built controlling for confounders. Survival time for patients with palliative visits was only considered after initial OPCC. Statistical significance was defined as p < 0.05. The study had institutional IRB approval. Results: Our cohort consisted of 1,114 patients with non-small cell lung cancer, 55% of whom were metastatic at diagnosis. 6% (n = 70) of the patients had an OPCC at some point after their diagnosis. When controlling for stage at diagnosis and age, OPCC was associated with an adjusted hazard ratio of 0.57 (95% CI 0.34-0.98). None of the patients with OPCC received ICI within 14 days of death compared to 6.5% of those without OPCC (p = 0.018). Similarly, only 2.9% of those with OPCC received ICI within 30 days of death, compared to 16.4% of those without OPCC (p = 0.003). Conclusions: In patients with lung cancer treated with ICI, OPCC was associated with improved OS regardless of age or stage at diagnosis. Our analysis also showed that patients who received OPCC were less likely to receive ICI near the end of life. It is possible that OPCC may prolong survival by decreasing the ineffective use of aggressive care at the end of life. Further research is needed to clarify the relationship between OPCC and cancer outcomes.

BACKGROUND:Prior research indicates a connection between immune-related adverse events (irAEs) and improved progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer. However, limited data exists for extensive stage small cell lung cancer (ES-SCLC). METHODS:This study included all ES-SCLC patients who received at least one dose of an immune checkpoint inhibitor between 2 January 2011 and 4 July 2022 using a large retrospective registry from a single institution. PFS and OS were right-censored at the date of last follow-up and were estimated using the Kaplan-Meier method. Differences in PFS and OS between irAE groups were assessed using Cox proportional hazards models. RESULTS:Among 245 patients with ES-SCLC; 56 (23%) experienced irAEs, 24 (42.9%) of which were high-grade (3-4). High-grade irAEs occurred at a median of 1.2 months (interquartile range [IQR] 0.45-2.5), while low-grade irAE occurred at 2.8 months (1.3-5.2). PFS was significantly longer among any irAE vs none (HR = 0.49; [95%CI 0.32-0.77]) as was OS (HR = 0.49; [95%CI 0.34-0.72]). CONCLUSIONS:In ES-SCLC patients treated with immunotherapy, those who experienced any irAE demonstrated a two-fold increase in both PFS and OS compared to those without an irAE. This is consistent with other tumor primaries.

2540 Background: For many tumor types, there is an option to start an immune checkpoint inhibitor (ICI) at the time of diagnosis or to sequence ICI after chemotherapies or targeted therapies. The risk of immune-related adverse events (irAE) may vary by the line of therapy. Prior systemic therapies might release cancer epitopes and increase the risk of an irAE through awakened subclinical autoimmunity. Conversely, prior systemic therapies may lead to residual immunosuppression and reduce the risk of irAEs. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. Study personnel reviewed the electronic medical record and defined irAEs according to Common Terminology Criteria for Adverse Events. Research specialists at Vasta Global captured most clinical outcomes. Line of therapy was defined ordinal manner, with four or more combined into a single group due to data sparsity. A multivariable logistic regression model was built to assess effect of line of therapy on any irAE while controlling for confounders identified either a priori or in univariate analysis. Given potential for heterogeneity, interaction between tumor primary and line of therapy was tested. SAS v9.4 was used for all analyses. Results: Among the final cohort of 3,101 patients, 1,169 (38%) were noted to have an irAE of any grade. ICI were used as first-line therapy in 1,432 patients and second-, third-, or at least fourth-line in 1,119, 328, and 222 patients, respectively. The most common tumor type was non-small cell lung cancer (36%), followed by melanoma (14%). At baseline, any-grade irAE were more common among first-line ICI with 618 (43.2%) than for second-line (395, 35.3%), third-line (102, 31.1%), or at least fourth-line (54, 24.3%; p<0.01). After adjusting for age (over 65), sex, smoking history, and body mass index, the model revealed significant heterogeneity, indicated by a significant interaction between the ICI line and the primary tumor type (p=0.01). The impact of the ICI line on the odds ratio (OR) of irAE for each primary calculated: melanoma (OR) 0.54 (95% confidence interval [CI] 0.32-0.93), non-small cell lung cancer OR 1.14 (CI 0.96-1.35), head-neck cancer OR 0.82 (CI 0.58-1.14), and renal cell carcinoma OR 0.78 (CI 0.57-1.06). Conclusions: The effect of pre-treatment with prior systemic therapy was significantly associated with the odds of developing an irAE, though this effect was significantly heterogeneous between tumor primaries. Melanoma was significantly less likely to develop irAE when heavily pre-treated. In contrast, NSCLC suggested a trend of increased odds of irAE with more pre-treatment however it was not statistically significant. Further study is indicated to clarify the types of prior systemic therapy that may modulate the risk of irAE and better clarify the optimal sequencing of ICI.

e13744 Background: Disparities due to socioeconomic status persist in the treatment of cancer. Newer therapies, such as immune checkpoint inhibitors (ICIs), offer easier administration, lower risk of toxicity, and may improve accessibility compared to cytotoxic chemotherapy. Prior studies on ICI outcomes have shown mixed results at the county level, and there is a need to investigate social determinants of health at a more granular level. Our study aims to compare long-term ICI outcomes between socioeconomic groups at the census tract level among patients with cancer. Methods: The investigators compiled data from 2/1/2011 to 4/7/2022 on patients who received at least one dose of an ICI at a comprehensive cancer center and its outreach clinics to create a retrospective patient registry. Investigators used a secure, cloud-based REDCap registry, validated it with data quality rules, and resolved discrepancies. Clinical research specialists at Vasta Global captured most of the data. Investigators correlated patients’ ZIP codes with 2010 US Department of Agriculture Rural-Urban Commuting Area (RUCA) classifications and census tracts with 2020 Center for Disease Control Social Vulnerability Index (SVI) data. The univariate analyses used the ANOVA or Kruskal-Wallis tests, chi-square tests, and Kaplan-Meier methods. The multivariate analyses used Cox and logistic regressions, adjusting for age, race, ethnicity, type of cancer, smoking status, age-adjusted Charlson Comorbidity Index, and other comorbidities. Results: Our cohort consisted of 1,807 patients who were an average of 66 years old, predominantly male (60.8%), white (84%), non-Hispanic (98%), and had lung cancer (45.1%) as the most common tumor type. Univariate analyses found no associations between either RUCA or SVI and overall survival (OS), progression-free survival (PFS), immune-related adverse events (irAE), or time to irAE. For RUCA, multivariate analysis found that rural location of residence was associated with shorter PFS (all covariates, p 0.0386). For SVI, multivariate analysis showed no significant association with OS, PFS, number of irAEs, or time until irAE (including high-grade irAEs). Conclusions: Rural residence by ZIP code was associated with shorter PFS, indicating that there may be decreased access to ICI for these patients. However, the overall findings suggest similar ICI treatment outcomes across patients with widely variable social determinants of health by census tract. Further research is needed to understand how newer therapies can be best positioned to overcome disparities in cancer care.

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This study characterized the frequency, severity, patterning and timing of NAEs using a large retrospective registry, including all patients who received at least one dose of an ICI from 2/1/2011-4/7/2022 within our health network. Results: Among 3137 patients, there were 54 NAEs (1.72% any grade; 0.8% grade 3-4). Most NAEs were peripheral (57.4%) versus central (42.6%). Melanoma and renal cell carcinoma were significantly associated with NAEs. Conclusion: The incidence of NAEs was rare though higher than many prior case estimates; the timing was consistent with other AEs. NAEs frequently occurred in tumor types known to favor brain metastases. Immune checkpoint inhibitors are new drugs for cancer. They boost your body's defenses to fight cancer cells. These drugs can be used alone or with other cancer treatments. Most people are okay with these medicines, but some might have problems in different parts of the body. This can be tricky to figure out. Rarely, there can be issues in the brain or nerves. These side effects are rare, happening in about 2 in every 100 people who use the drugs. They are more common in certain cancers like melanoma and kidney cancer. As doctors learn more about these side effects, they can better predict, treat, and prevent them.

e14701 Background: Medical providers often describe concerns about a patient’s functional status in routine clinical documentation (e.g., hard of hearing, recent falls, difficulty with home medication). These clinician-documented pretreatment functional variables (PFVs) may be predictive of outcomes among patients receiving immunotherapy. The goal of this retrospective study is to check for an association between the documentation of PFVs with overall survival (OS), progression-free survival (PFS), and the incidence of immune-related adverse events (irAEs). Methods: We created a retrospective registry of all patients who received at least one dose of an immune checkpoint inhibitor for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center. The investigators created a validated REDCap registry; clinical research specialist at Vasta Global captured most data. PFVs were collected by review of routine clinical documentation 30 days before or after the first dose. Patients were stratified by their number of PFVs (0,1, or 2+) and by their age (≥ or <65 years). PFVs assessed function, nutritional status and social support and were dichotomized to indicate impaired vs not with ten total categories. We used Cox proportional hazard modeling for survival analyses between the three PFV groups, calculated from the first dose of immunotherapy to disease progression, death, and last known follow-up controlling for age, BMI, smoking, and disease type with a two-sided alpha of 0.05. Results: From the overall cohort (n = 3,101), 35% had no PFVs, 32% had one PFV, and 32% had two or more PFVs; 52.5% were considered younger, and 47.5% geriatric-aged (≥65yo). PFVs were more common among the geriatric-aged population (mean 1.43 vs 0.89). The most common cancer types were lung cancer (45%), melanoma (14%), and kidney (6%). The most noted PFVs were visual impairment (26%), unintentional weight loss (22%), inability to walk a quarter block (17%), living alone (16%), and falls (14%). In the overall population, an increasing number of PFVs was associated with shorter OS. When stratified by age, the number of PFVs was associated with shorter progression-free survival (p <0.01) and overall survival (p <0.01) among the geriatric and non-geriatric populations (Table). There was no association between increasing PFVs and incidence of irAEs. Conclusions: Although often considered to be signs of aging, documentation of multiple PFVs was associated with worse OS and PFS among geriatric-aged and non-geriatric-aged populations. This study highlights the utility of routine clinical documentation on health status, including function, nutrition, and social support, to estimate survival regardless of chronologic age. [Table: see text]

Background: Immune checkpoint inhibitors (ICIs) have become common lines of therapy for genitourinary cancers (GUcs). Given their widespread use, understanding the risk factors, comparative profiles, and timing of immune-related adverse events (irAEs) is essential. Methods: We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 1 February 2011 and 7 April 2022 at a comprehensive cancer center and its outreach clinics. Dichotomous outcomes were modeled using multivariable logistic regression. Survival outcomes were compared using multivariable Cox regression. Results: Among 3101 patients, 196 had renal cell carcinoma (RCC) and 170 had urothelial tumors. RCC patients were more likely to experience irAEs (OR 1.78; 95% CI 1.32–2.39), whereas urothelial carcinoma patients were not (OR 1.22; 95% CI 0.88–1.67). RCC patients were more prone to dermatitis, thyroiditis, acute kidney injury, and myocarditis, compared to other tumors, while urothelial carcinoma patients were not. The impact of irAEs on survival was not significantly different for GUcs compared to other tumors. Conclusions: RCC primaries have a significantly different irAE profile than most tumors, as opposed to urothelial primaries. Further, RCC was more likely to experience any irAEs. Heterogeneity of survival benefits by irAEs was not seen.

Background Immune checkpoint inhibitors (ICI) have a high frequency of any-grade immune-related adverse events (irAEs) that can involve multiple organs. Similar to EGFR inhibitors, dermatological adverse events may be predictive of efficacy. Additional data is needed to guide the decision to continue, defer, or switch therapy when these irAEs occur. Methods We created an IRB-approved retrospective registry of all patients who received at least one dose of an ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. Study personnel reviewed the electronic medical record, captured all treatment-emergent adverse events that were in routine clinical documentation, and estimated attribution and severity using the Common Terminology Criteria for Adverse Events. Case report forms were stored in REDCap and validated with data quality rules; research specialists at Vasta Global captured most clinical outcomes. Time variables were censored at the date of last follow-up. A multivariable Cox proportional hazards model was built. The proportional hazards assumption was validated graphically. SAS v9.4 was used for all analyses. Results The final cohort included 3141 patients, of which 1176 (37.4%) experienced at least one irAE. 267 (8.5%) of all patients experienced a dermatological irAE; and among them, 153 (57.3%) also experienced a second, non-dermatological irAE. Melanoma and renal cell carcinoma were the two most likely primary tumors to experience dermatological plus second irAE with 12.1% and 10.2% respectively compared to the incidence of 3.8% among all other tumor primaries (p<0.01; p<0.01). Among patients with dermatological plus a second irAE, the first events occurred sooner (median 1.4 months) than either separately (median 2.1 and 2.1 months respectively). When modeled to control for age, tumor primary, and stage, the patients with dermatological plus a second irAE conferred the highest survival benefit compared to no event (HR 0.27; 95% CI 0.20–0.28) (figure 1). Conclusions In this study, the pattern of irAEs were shown to be meaningful in the context of survival. Over half of patients with dermatological irAEs experienced another system irAE. These patients experienced a shorter time to the first event and a more prolonged overall survival than the other study groups, suggesting a robust response. Further studies should investigate this sub-population to identify a potential genomic or biomarker indicator for hyper-responsiveness to immunotherapy.

12061 Background: Comorbidities are more prevalent among older adults and predict worse outcomes for cytotoxic chemotherapy. Immunotherapies are increasingly used to treat various cancers and have a milder but less predictable toxicity profile. This study aimed to evaluate the association of comorbidity burden with immune-related adverse events (irAEs) and survival among older adults treated with these immunotherapies for any cancer type. Methods: We created a retrospective registry of consecutive patients ≥ 70 years old treated with one or more doses of an immune checkpoint inhibitor for any cancer indication between 2/1/2011- 4/7/2022 at our comprehensive cancer center. Treatment outcomes, including treatment-emergent adverse events, were captured via chart review. The comorbidity burden at the time of immunotherapy initiation was captured by chart abstraction and classified using the Charlson Comorbidity Index (CCI). We compared patients with high CCI scores (≥ 4) to patients with low CCI scores (CCI <4) on the outcome of any irAE yes/no, using chi-square tests. We used the Kaplan-Meier method to compare progression-free survival (PFS) and overall survival (OS) between the two CCI groups. Survival analyses were calculated from the first dose of immunotherapy to death, last follow-up, or disease progression. A two-sided alpha of 0.05 was used for analyses. The study had institutional IRB approval. Results: Our cohort consisted of 1,216 patients (median age 76 years [interquartile range 73 to 80]), of which 217 (18%) had a high CCI score. The most common comorbidities were chronic obstructive lung disease (45%), coronary artery disease (29%), and diabetes (29%). The most common cancer type was lung cancer (46%), followed by melanoma (15%). Patients with a high CCI score had a shorter median overall survival than patients with a low CCI (11.2 vs. 13.8 months, respectively, p = 0.049). However, there was no significant difference in PFS between the high and low CCI groups (median PFS 27.1 vs. 25.0 months, p=0.32). There was no association between the CCI group and the incidence of any-grade irAEs (39% vs. 40%, p = 0.82). There was also no association between CCI group and high-grade (grade ≥3) irAEs (17% vs. 15%, p = 0.35). We did not find any associations between any individual CCI comorbid condition and risk of irAE. 1 Conclusions: A high comorbidity burden, as measured by the CCI, was not associated with increased immunotherapy toxicity or shorter PFS among older adults. The presence of comorbidities was associated with shorter OS. These data can support informed decision-making for older adults with comorbidity considering immunotherapy. Reference: 1. Charlson ME, Carrozzino D, Guidi J, Patierno C. Charlson Comorbidity Index: A Critical Review of Clinimetric Properties. Psychother Psychosom. 2022;91(1):8-35. doi: 10.1159/000521288. Epub 2022 Jan 6. PMID: 34991091.

Background Despite being a groundbreaking cancer therapy, immune checkpoint inhibitors (ICI) can lead to potentially life-threatening toxicity with checkpoint inhibitor pneumonitis (CIP). While treatable, it is easy for clinicians to miss the symptoms of CIP, which can lead to a delay in diagnosis and worsening respiratory function. There is no consensus approach to systematically identifying patients at risk of developing CIP. Thus, we sought to create a workflow that could inform patient selection for ICI therapy based on previously reported risk factors for CIP development. Materials and methods We retrospectively identified 250 patients with lung cancer treated with at least one dose of an ICI over 20 months. Data were collected on comorbidities, cancer type and stage, performance status, ICI cycles, biomarkers, prior curative treatment, diagnostic evaluation, antibiotics, steroids, progression, and survival. A single-blinded radiologist characterized radiographic patterns of suspected CIP cases. Results Among 97 patients who received steroids while admitted to the hospital, 12 (6%) had at least one sign or symptom suggestive of CIP. Chronic obstructive pulmonary disease and non-small cell lung cancer subtypes correlated with suspicion of having CIP. CIP was confirmed in five patients (42%) and ruled out (mimics) in seven (58%). Median times until symptoms were 17 months and one month for confirmed and mimic cases, respectively. The median time to confirm or exclude CIP was 5 ± 4 days. Most suspected cases underwent thoracic imaging, blood cultures, and empiric antibiotics. Radiographic patterns in suspected cases included ground glass opacities, organizing pneumonia, acute interstitial pneumonia/acute respiratory distress syndrome, bronchiolitis, radiation recall pneumonitis, hypersensitivity pneumonitis, and post-radiation fibrotic changes. Conclusions CIP mimics are common in clinical practice; therefore, it is reasonable to empirically treat suspected cases with shorter courses of steroids until diagnostic clarity is achieved. This proof-of-concept study demonstrates that this novel workflow can identify the true incidence of CIP, inform treatment decisions, and lead to the development of implementation studies to improve patient care directly.

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 < 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.