Citations

TPS2092 Background: Glioblastoma (GBM) is the most common primary brain malignancy in adults. GBM is universally recurrent and associated with dismal outcomes. Re-irradiation (reRT) is ideal for evaluating combination therapy for recurrent GBM (rGBM) due to its multifactorial mechanism of action, including downstream immunomodulatory activity. RT (especially multi-fraction) increases immunogenicity in preclinical models by promoting immune activation, immune migration, and antigen uptake. Additionally, a recent study demonstrated enhanced PD-L1 expression in the glioma tumor microenvironment (TME) following RT, and combining stereotactic RT with a PD-1 inhibitor improved survival in murine models. Retifanlimab is a humanized monoclonal anti-PD1 IgG4 antibody that received FDA approval for adults with metastatic or recurrent locally advanced Merkel cell carcinoma. Bevacizumab, an anti-VEGF antibody, is a treatment for radiation necrosis/cerebral edema with less immune suppression than corticosteroids. In a previous Phase 2 study, hypofractionated RT (HFRT), retifanlimab, and bevacizumab was associated with a 9-month overall survival (OS) rate of 71.4%. To demonstrate the efficacy of this regimen compared to HFRT and bevacizumab, we have designed a new randomized controlled Phase 2 trial. We hypothesize that combination reRT with retifanlimab will produce a more robust anti-tumor immune response and improve OS compared to reRT without retifanlimab. Methods: This is a multicenter, open-label, randomized, controlled Phase 2 study of retifanlimab, bevacizumab, and HFRT for adult patients with rGBM. Patients are randomized 1:1 to the experimental (bevacizumab + retifanlimab + HFRT) or control cohort (bevacizumab + HFRT). Key eligibility criteria include age ≥ 18 years, Karnofsky performance status ≥ 60, ≥ 4 months since administration of any prior bevacizumab, and dexamethasone dose ≤ 4 mg at the time of randomization. The primary endpoint is 9-month OS. Secondary endpoints include OS, progression-free survival, objective response rate, neurologic assessment by NANO criteria, and adverse events profile. Protocol treatment will continue up to two years, or until progression or intolerable toxicity. Survival follow up will continue every two months, up to four years. Seven of the planned 94 patients have been enrolled as of submission on 1/28/25. Clinical trial #: NCT06160206. Funding provided by Incyte. Clinical trial information: NCT06160206 .

7032 Background: The impact of immune cell counts pre LD and during immune reconstitution on CAR T therapy outcomes is poorly understood. We investigated the association between CD4, CD8 and NK cell counts and CAR T therapy outcomes in patients with LBCL. Methods: Retrospective study of R/R LBCL patients who received CAR T cells between 2016-24 at Mayo Clinic, Rochester, were included in this analysis. Peripheral blood CD4, CD8 and NK counts were measured pre LD and at M1 post CAR T infusion. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff for pre LD and M1 immune cells to predict patients who were alive and in remission at 6 months (M6) post CAR T infusion. Patients who progressed or were lost to follow up prior to day 30 were excluded from M1 ROC analysis. Results: Of 140 patients, 81 were alive and in remission at M6 (Group A), while 59 had relapse or death (Group B). Axicabtagene ciloleucel was the CAR T product given in 81% of patients (114/140). Median pre LD CD4 counts were significantly lower in Group B compared to group A (143 vs 280 cells/µL, p = 0.001). No significant difference was observed in median pre LD CD8 counts (205 vs 221 cells/µL, p = 0.8). ROC analysis identified an optimal pre LD CD4 count of 124.5 cells/µL for M6 alive+remission. Lower pre LD CD4 counts (<124.5) predicted worse progression free survival (PFS) in univariate (HR = 3.02, 95% confidence interval [CI]: 1.73–5.27, p< 0.01) and multivariable analysis (MVA) adjusted for IPI and the number of prior lines (aHR = 2.54, 95% CI: 1.39–4.62, p< 0.01).Lower pre LD CD4 counts also predicted inferior overall survival (OS) in MVA (aHR = 2.27, 95% CI: 1.08–4.77, p = 0.03). (Table 1) On day 30 landmark analysis, ROC identified M1 optimal CD4 count of ≥ 99.5 cells/µL to be associated with a trend toward superior PFS (P=0.09), but not OS (p=0.90) in MVA. Median pre LD NK cell counts were significantly lower in Group B (73 vs 98 cells/µL, p = 0.04). ROC analysis identified an optimal pre LD NK count of 151 cells/µL for M6 alive + remission. Lower pre LD NK counts (<151) predicted worse PFS, both on univariate (HR = 4.17, 95% CI: 1.29–13.47, p = 0.02) and MVA (aHR = 4.64, p< 0.01). The lower pre LD NK cell count group had worse OS in MVA (aHR = 5.69, 95% CI: 1.16–28.1, p = 0.01). (Table 1) On D30 landmark analysis, M1 NK cell count of ≥ 128.5 cells/µL was associated with a trend toward superior PFS (P=0.08), but not OS (p=0.30) in MVA. Conclusions: Pre LD CD4 and NK cell counts are significantly associated with PFS and OS post CAR T therapy in patients with R/R LBCL. Pre-treatment immune subset levels may identify patients at higher risk of relapse or death after CAR-T therapy. Groups Median PFS 2 Year PFS Median OS 2 Year OS CD4 ≥124.5 cells/µL (N=75) NR 58% 3.31 years 67% CD4 <124.5 cells/µL (N=30) 2.2 months 22% 1.59 years 45% NK ≥151 cells/µL (N=17) NR 77% NR 84% NK <151 cells/µL (N=82) 10.6 months 44% 3.31 years 62%

7023 Background: Axi-cel is an autologous chimeric antigen receptor (CAR) T-cell therapy approved for adults with R/R LBCL after ≥ 1 prior line of therapy (LoT). Adverse events, such as cytokine release syndrome (CRS) and neurologic events (NEs), may deter centers from using axi-cel in an outpatient (OPT) setting, though individual centers have observed comparable safety and effectiveness in OPT and inpatient (IPT) care (Furqan et al. Blood Adv . 2024). Here, we present safety and effectiveness outcomes of axi-cel by intention to treat in OPT and IPT settings in a multicenter real-world dataset. Methods: Pts receiving axi-cel for R/R LBCL in the US from 01/2021-07/2023 with data in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry were eligible for analysis. Pts with prior allogeneic transplant or unknown intended care setting were excluded. Of potential pts, 119 OPT pts were identified from 29 centers where an increasing trend was seen (9.6% of pts in 2021 were OPT, 13.5% in 2022, 22.8% in 2023). Pts were matched to 119 IPT pts by propensity score matching on age, sex, comorbidities, lactate dehydrogenase (LDH), bulky disease, prior LoT, chemosensitivity, and infusion year (see table). Results: OPT pts had median age of 63 y (25% ≥ 70), 66% were male, and 67% had ≥ 1 comorbidity. Half (50%) had elevated LDH and 73% had 1 prior LoT. Bulky disease was reported in 3%, and 60% had chemo-resistant disease. Outcomes were analyzed at median follow-up of 12 mo. Safety and effectiveness outcomes were similar between OPT and IPT pts (see table). In multivariate analyses, no differences were found between intended care setting and CRS (odds ratio [OR] 1.09 [95% CI 0.51-2.35]), CRS Gr ≥ 3 (OR 0.57 [0.12-2.60]), NEs (OR 1.14 [0.65-2.00]), or NEs Gr ≥ 3 (OR 0.98 [0.48-2.00]). Among OPT pts, 24% and 50% did not require hospital admission within 30 d and 3 d, respectively. In pts aged ≥ 70 y, only any Gr NEs were higher in the OPT group. Conclusions: After matching on key factors that may be used to select pts for OPT infusion, outcomes were comparable between intended care settings. These findings corroborate prior results and support the consideration of axi-cel in appropriate OPT care settings. Outcomes between matched pts with R/R LBCL receiving axi-cel intended for OPT or IPT. OPT (n=119) a IPT (n=119) a CRS any Gr / Gr ≥ 3 83 (75−89) / 3 (<1−7) 83 (74−89) / 4 (1−10) NE any Gr / Gr ≥ 3 47 (38−57) / 19 (12−27) 46 (37−56) / 21 (14−30) Overall / complete response rates 78 (69−85) / 68 (59−76) 76 (67−83) / 62 (52-70) Duration of response @ 12 mo 64 (52−74) 69 (58−78) Progression-free survival @ 12 mo 53 (43−62) 53 (43−61) Overall survival @ 12 mo 71 (61−78) 72 (62−79) Non-relapse mortality @ 12 mo 6 (2−11) 4 (1−8) Hospital admission within 30 days of infusion / median duration (range), d 76 (67−83) / 9 (2−53) Not Applicable a Percent (95% CI) unless otherwise specified.

7018 Background: CAR-T cell therapy represents a notable advancement in treating relapsed/refractory (R/R) hematological malignancies. Adverse events include CRS, infections, and neurological and cardiac complications. While there are reports from major academic institutions on the adverse effects of CAR-T therapy, we used data from the National Inpatient Sample (NIS) to gather national estimates of complications related to CAR-T therapy. Methods: A retrospective study was conducted to analyze patients who underwent CAR-T cell therapy by utilizing appropriate ICD-10-PCS procedure codes (XW033C3, XW043C3, XW23346, XW24346, XW23376, and XW24376) from NIS 2019 to 2021. Data regarding infections, toxic encephalopathy (a surrogate for neurological toxicity), and adverse cardiac events were extracted using relevant ICD-10-CM diagnostic codes. Patients experiencing various grades of CRS were identified through specific ICD-10 codes available in 2021 (Grades 1-5: D89.831-D89.835). Results: This study analyzed 6515 patients who underwent CAR-T cell therapy from January 2019 to December 2021. Among them, 60.7% were male. 74.6% were Caucasian, 11.7% were Asian and 6.7% were African American. 49.8% of patients had private insurance, 36.2% had Medicare, and 8.6% had Medicaid. 6.8% of patients were diagnosed with pneumonia, while sepsis occurred in 7.4% of patients and 3% experienced septic shock. 19.4% of patients experienced cardiac arrhythmias, and major cardiovascular events were recorded in 4.7% of the cohort. Acute myocardial infarction and stroke were documented in 0.6 and 1.2% of patients, respectively. Toxic encephalopathy was reported in 19.7% of patients. Among 2235 patients identified to have received CAR-T in 2021, 59.7% developed CRS. Grade 1 and grade 2 CRS were reported in 32% and 21% of patients, respectively, while grade 3 and grade 4 reactions were noted in 4.7% and 2% of patients, with no cases of grade 5 identified. The mean total cost of hospitalization was 308,364$, and the mean length of hospital stay was 19.5 days. The overall in-hospital mortality rate was 3.4%. Conclusions: Our study describes real-world outcomes from a large dataset of CAR-T patients. Infections pose a significant challenge with CAR-T therapy, highlighting the importance of early detection and timely antimicrobial treatment. CRS is common, with a 60% incidence, similar to previous clinical trials (55%). Immediate management is crucial for addressing CRS toxicity. Adverse neurological and cardiovascular incidents are often reported, emphasizing the need for meticulous monitoring and coordinating multidisciplinary care plans. The financial burdens also bear mentioning: CAR-T therapy costs significantly higher than autologous stem cell transplants. Further studies to address these issues are warranted.

7014 Background: Mosun is a CD20xCD3 bispecific antibody that can be administered in the outpatient setting for a fixed duration. Intravenous Mosun is approved for the treatment of relapsed/refractory FL after ≥2 prior lines of therapy. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We report the efficacy and safety of Mosun SC in patients with previously untreated high-tumor burden FL in the Phase II MorningSun study (NCT05207670). Methods: Patients with previously untreated high-tumor burden FL, per GELF criteria, were enrolled into this cohort. Mosun SC was administered with step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) then 45mg on D1 for up to 17 cycles (1 year; 21-day cycles). Patients with a partial or complete metabolic response (CMR) after C17 could receive additional Mosun maintenance therapy (45mg every 8 weeks for up to 1 year). Corticosteroid prophylaxis to reduce the risk of cytokine release syndrome (CRS) was mandatory in C1–2 and optional thereafter. The primary endpoint was progression-free survival (PFS) rate at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), and safety. Results: As of May 29, 2024, 102 patients were enrolled; 55 patients had completed initial treatment (17 cycles), 31 had discontinued (most commonly due to progressive disease [n=19] and adverse events [AEs; n=4]), and 16 were ongoing initial treatment. Forty-two patients received maintenance treatment, and this was ongoing in 38 patients. Median age was 65 years (range: 24–86); 52.0% of patients were female. Most patients had Ann Arbor stage III/IV (91.2%) and a FLIPI score ≥2 (78.4%). Median duration of follow-up was 13.9 months. The 12-month PFS rate was 82.8% (95% confidence interval [CI]: 73.0–89.3). ORR was 87.3%; 60.8% of patients had a CMR. Among the 89 patients with a response, the median TTR was 2.7 months (range: 1.2–5.8). The most common AEs (≥30%) were injection-site reaction (57.8%), fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 AEs and serious AEs (SAEs) were reported in 44.1% and 29.4% of patients, respectively. CRS events were all Grade 1/2 and SAE of CRS occurred in 10.8% of patients (Table); all events resolved. Conclusions: Mosun SC demonstrated promising efficacy in patients with previously untreated high-tumor burden FL. The manageable safety profile, including rate of CRS, supports the administration of fixed duration Mosun SC in an outpatient setting. Additional data, including cytokine profiling and T/B/NK dynamics, will be presented. Clinical trial information: NCT05207670 . CRS events, n (%) PatientsN=102 Any grade 35 (34.3) Grade12 30 (29.4)5 (4.9) SAE 11 (10.8) ManagementSteroidsTocilizumabSteroids + tocilizumabFluidsICU admission 8 (7.8)6 (5.9)3 (2.9)3 (2.9)2 (2.0)

10556 Background: The coexistence of interstitial lung diseases (ILD) and lung cancer (LC) presents a clinical challenge. ILD, including idiopathic pulmonary fibrosis (IPF) and non-IPF entities, is associated with an elevated risk of LC. However, the clinical features, treatment patterns, and survival outcomes of ILD-LC, especially IPF-LC, remain underexplored. We aimed to comprehensively evaluate survival outcomes and risk factors for mortality of ILD-LC patients based on a real-world long-term clinical cohort. Methods: A total of 1,341 eligible patients for this study were drawn from the Epidemiology and Genetics of Lung Cancer research program database (Mayo Clinic) including 96 IPF-LC, 111 Non-IPF ILD-LC, 99 ILD-only, and 1,035 propensity-matched LC-only patients (Controls). Data were collected on demographics, comorbidities, tumor features, treatment, and patient outcomes. Survival analyses used Kaplan-Meier methods; risk factors were assessed via Cox Proportional Hazards models. All comparisons reported below were statistically significant with p-values≤0.001 unless specified. Results: Among the 20,470 primary LC patients who were diagnosed from 1997 through 2016 and followed to 2021, 207 (1.0%) had ILD-LC, of which 96 (46.4%) had IPF. Comparing to Controls, ILD-LC patients were 4 years older at the time of LC diagnosis, 63.8% (vs. 52.8%) male, had a higher rate of former smokers (60.4% vs. 47.3%), a lower proportion of adenocarcinoma (37.7% vs. 57.5%), and a higher proportion of squamous cell (28.0% vs. 20.3%) and small cell carcinoma (13.5% vs. 8.4%). Although no significant differences in either LC stage or grade, ILD-LC patients had a significantly higher mortality rate (90.3% vs. 78.8%), particularly among IPF-LC patients (97.9% vs. 83.8%). ILD-LC patients were less likely to undergo surgery or receiving pharmacological treatments (73.9% vs. 93.5%). The median 5-year overall survival rate (OS, months) were 49.5 for Controls, 35.2 for Non-IPF ILD-LC patients, and 15.9 for IPF-LC patients. Analysis of six most common comorbidities revealed that pulmonary hypertension was associated with worse OS in ILD-LC patients compared to those without it (11.9% vs. 20.1%, P < 0.05); however unexpectedly, hypertension in ILD-LC patients was associated with better OS (21.3% vs. 14.4%) and emphysema in IPF-LC patients with better OS (7.9% vs. 3.4%, P < 0.05) when compared to those without the two comorbidities, respectively. Conclusions: This study highlights the poorer survival outcomes in ILD-LC patients, particularly IPF-LC patients, emphasizing the need for further investigation into optimized therapies and comorbidity management. Our findings also call for attention to two unexpected associations of hypertension and emphysema, warranting in-depth research on the possible biological and physiological mechanisms.

10544 Background: Incorporation of Polygenic Risk Scores (PRS) can refine traditional breast cancer risk assessment models to provide precise estimates of breast cancer risk. However, the impact of such an integrated model on clinical decision-making related to breast cancer surveillance and preventive strategies is not fully understood. Methods: The GENRE-2 is a prospective single-arm multisite clinical trial (NCT04474834) incorporating PRS into standard breast cancer risk assessment models to determine the impact of PRS on clinical decisions on breast cancer prevention and surveillance. Women at high risk of breast cancer due to NCI-BCRAT 5-year risk of ≥ 3%, or IBIS (Tyrer-Cuzik) 10-year breast cancer risk of ≥5%, biopsy-proven high-risk breast lesion, or a pathogenic variant (PV) in ATM , BRCA1, BRCA2, CHEK2 or PALB2 , were enrolled from five sites in the United States. All women were invited to complete surveys on their breast surveillance and cancer prevention decisions based on pre-PRS standard risk models and post-PRS risk estimation, and further annual surveys are planned for 10 years. Results: Among 902 women enrolled in the study, 605 (median age: 52 years) received PRS results and completed a survey to date. Of those who received PRS results,195 (32.2%) were PV carriers. Among non-carriers, the median 10-year and lifetime pre-PRS IBIS-based risk was 10.0% and 28.7%, respectively. Among PV carriers, the CanRisk-based 10-year and lifetime pre-PRS risk estimates were 6.3% and 25.2% for ATM , 22.3% and 77.6% for BRCA1 , 18.5% and 77.7% for BRCA2 , 7.1% and 25.7% for CHEK2 , and 16.8% and 38.0% for PALB2 PV carriers, respectively. After the incorporation of PRS, the lifetime risk of breast cancer increased by at least 10% in 31% of non-carriers and 7.7% of PV carriers and decreased by at least 10% in 10.7% of non-carriers and 7.7% of PV carriers. The proportion of non-carriers with lifetime risk < 20% or > 40% changed from 17.3% and 22.0%, respectively, in the pre-PRS evaluation to 24.4% and 32.9%, in the post-PRS evaluation. A higher lifetime post-PRS score was associated with intent to take preventive action (surgery or endocrine agents). In non-carriers, the proportion of women with a lifetime risk < 20% with intent to take preventive action was 11%, compared to 36.8% of those with a lifetime risk > 40% (p < 0.001). Similarly, in PV carriers, the proportion of women with lifetime risk < 20% with intent to take preventive action was 20.8% compared to 41.1% of those with lifetime risk > 40% (p = 0.015). Conclusions: The GENRE-2 trial demonstrates that the incorporation of PRS into breast cancer risk assessment models in high-risk women is feasible and leads to clinically meaningful changes in breast cancer risk estimates and decision-making regarding preventive strategies. Evaluation of the implementation of breast cancer risk management strategies in study participants is ongoing and will be reported. Clinical trial information: NCT04474834 .

e15682 Background: Small cell carcinoma (SCC) of gastrointestinal tract is a highly aggressive rare malignancy with an estimated prevalence of 0.1% to 1% of all GI neoplasms. Treatment and survival outcomes data are very limited. Here we present an analysis of outcomes of patients with intestinal SCC using data from the Survival, Epidemiology, and End Result (SEER) database. Methods: SEER (2000-2020) was used to identify patients with SCC involving of the small intestine, colon and rectum. Variables included age, race, site, stage, chemotherapy (chemo), radiation therapy (RT) and surgery. Cox regression was used to model survival outcomes based on site, stage, and treatment received in the overall group and stage subgroups. Results: 1,169 patients with SCC of the small intestine, colon, and rectum were identified. Median age was 65 (24-90). 631 (54%) were male; majority of patients were white (989; 85%), followed by black (128; 11%) and other races (50; 4.3%). Colon (569; 49%) and rectum (514; 44%) were the predominant sites while small intestine only comprised 7.4% of the patients. Distant, regional and local diseases were reported in 55%, 17% and 7.5% of the patients. Median overall survival (mOS) of the entire group was 8 months (m). Primary tumor sites of small intestine and rectum were significantly associated with lower mortality rate in comparison to colon (11 m and 9 m vs 5 m, p < 0.001 for both). Patients with localized disease had the lowest mortality rate when compared with those with regional or distant metastatic diseases (38 m vs. 16 m and 5 m, p < 0.001 for both). Receiving surgery (HR: 0.458, p < 0.001), chemo (HR: 0.473, p < 0.001), and RT (HR: 0.733, p = 0.003) were all significantly associated with lower mortality rate (Table). These differences remained significant in each stage-based subgroup except for chemotherapy in localized disease subgroup, which encompassed only 87 patients. Conclusions: Intestinal SCC has poor prognosis, with SCC of the colon being most prevalent and with the highest mortality. Majority of patients presented with distant metastatic disease which led to high mortality. Multimodality treatment may improve survival for these patients. Number of cases (%) HR (CI) p-value mOS (months) vs reference Site (ref: colon) Rectum 514 (44%) 0.750 (0.648-0.867) <0.001 9 (ref: 5) Small intestine 86 (7.4%) 0.574 (0.44-0.749) <0.001 11 (ref: 5) Stage (ref: localized) Regional 201 (17%) 2.087 (1.507-2.891) <0.001 16 (ref: 38) Distant 639 (55%) 4.222 (3.110-5.733) <0.001 5 (ref: 38) Unknown/unstaged 242 (21%) 1.639 (1.160-2.315) 0.005 8 (ref: 38) Chemo (ref: none/unknown) Yes 590 (50%) 0.473 (0.404-0.553) <0.001 10 (ref:3) RT (ref: none/unknown) Yes 175 (15%) 0.733 (0.598-0.897) 0.003 12 (ref: 7) Surgery (ref: no surgery) Yes 363 (31%) 0.458 (0.385-0.546) <0.001 12 (ref: 6) Unknown 138 (12%) 0.717 (0.549-0.936) 0.01 7.5 (ref: 6)

e15673 Background: Since the late 1990s, both the incidence and mortality of invasive colorectal cancer (CRC) have decreased across the United States, including in Kentucky. Despite this, CRC incidence and mortality are above national average in Kentucky. Over the last two decades, a disparity in CRC incidence and mortality has emerged between Appalachian Kentucky (AK), a distinct eastern region, and Non-Appalachian Kentucky (NAK). This disparity is attributed to differences in social and structural determinants of health (SSDH) between these populations. Methods: Age-adjusted CRC incidence and mortality rates (2016-2020) for both Kentucky and the U.S. were obtained from the National Cancer Institute’s public database. Data from the Kentucky Cancer Registry were used to compare CRC incidence and mortality rates in AK and NAK counties from 1994-2021. Incidence rate ratio analyses across discrete time periods demonstrated statistical differences between these regions. Results: Compared to national data (2016-2020), Kentucky's CRC age-adjusted incidence and mortality rates were significantly higher: 45.9 vs. 36.5/100,000, 25.8%, for incidence, and 16.2 vs. 13.1/100,000, 23.7%, for mortality (both p < 0.0001). From 1995-2003 incidence and 1994-2003 mortality of CRC, were higher in NAK, these rates eventually decreased and equalized between NAK and AK. By 2010-2015 both incidence and mortality rates were higher in AK, 55.8 vs 48/100,000, 16.3%, (p = < 0.0001) and 20.1 vs 15.8/100,000, 27.2%, (p = < 0.0001) respectively. The most recent data (2016-2021) shows that these significant disparities persist, with AK’s incidence and mortality 51.8 vs 44.1/100,000, 17.5% (p = < 0.0001) and mortality 19.0 vs 15.1/100,000, 25.8% (p = < 0.0001) higher, respectively. Conclusions: While CRC rates have decreased nationwide and in Kentucky, a pronounced gap in both incidence and mortality has developed between Appalachian and Non-Appalachian Kentucky. Appalachian counties—which are more rural and impoverished—face greater barriers to accessing preventive healthcare, contributing to this disparity. Additionally, AK has higher rates of obesity, poverty, smoking, and lower educational attainment and screening rates. Recent public health efforts, such as promoting stool-based screening and increasing preventive care discussions, aim to reduce these disparities. However, delays in CRC screenings during the COVID-19 pandemic— resulting in approximately 1.7 million missed colonoscopies nationally— may have skewed the most recent data, necessitating further analysis in the coming years.

e15628 Background: Total neoadjuvant therapy (TNT) with cytotoxic chemotherapy and chemoradiation followed by surgical resection is a standard treatment for locally advanced rectal cancer (LARC). In a limited number of LARC patients with deficient mismatch repair (dMMR), treatment with an immune checkpoint inhibitor (ICI) resulted in all patients achieving complete clinical response (cCR) (median follow-up of 29 months) such that radiotherapy and surgery were avoided. These and other data have resulted in the routine use of neoadjuvant ICI for dMMR LARC. Here we report a multicenter series of patients with dMMR LARC treated with neoadjuvant ICI. Methods: Adult patients (N = 21) with dMMR LARC who received neoadjuvant ICI at Mayo Clinic, MD Anderson Cancer Center, Duke University or University of Pittsburgh were identified from the electronic medical record (EMR) and relevant data were abstracted. All patients were staged with pelvic MRI; clinical response was evaluated by repeat pelvic MRI and sigmoidoscopy. Data were summarized using descriptive statistics. This study was approved by the Mayo Clinic IRB. Results: Patients with clinical stage I (n = 2), II (n = 3) or III (n = 15) dMMR LARC were treated with neoadjuvant PD-1 monotherapy (n = 20) or combination (n = 1, ipilimumab+ nivolumab). Median age was 46 years (IQR 39, 65), 15 (71%) were male, 10 (48%) had distal tumors, and 14 had Lynch Syndrome. Median duration of ICI treatment was 7 mos (IQR 6, 12); one patient remains on dostarlimab at data cut-off. Clinical complete response (cCR) was achieved in 11 (52%) patients, partial response (PR) in 7 (33%), stable disease (SD) in 1 (5%), and progressive disease (PD) in 2 (10%) patients. Median time from first dose of ICI to best clinical response was 6 mos (IQR 5, 8) months. All partial or non-responders received salvage TNT with (n = 6) or without (n = 3) surgery. At a median follow up of 19 mos (range 6 to 56), tumor regrowth occurred in 1 patient who was subsequently treated with TNT. Any grade immune-related adverse event occurred in 6 (29%) patients; one grade 3 hepatitis occurred in the patient on Ipi+Nivo (Table1). Conclusions: Neoadjuvant ICI treatment of dMMR LARC resulted in half of treated patients achieving cCR. Careful monitoring is necessary to identify non responders who will require salvage TNT. Patient characteristics and clinical response to ICI. ID Sex Age Stage ICI Response to ICI ID Sex Age Stage ICI Response to ICI 1 M 62 T3N+ Pembro cPR 12 M 37 T3N+ Pembro cCR 2 M 60 T2N0 Pembro cCR 13 M 41 T3N0 Pembro cCR 3 M 80 T2N0 Pembro cPD 14 M 46 T4N+ Pembro cPR 4 M 36 T3N+ Ipi+Nivo cCR 15 M 68 T3N+ Pembro cPR 5 M 57 T3N+ Dostarli cCR 16 M 77 T3N0 Pembro cPR 6 M 39 T3N+ Dostarli cPR 17 M 40 T4Nx Pembro cCR 7 F 44 T2N+ Dostarli cPD 18 F 35 T3N+ Dostarli cCR 8 M 74 T3N+ Pembro cCR 19 M 60 T2N+ Pembro cPR 9 M 43 T3N+ Nivo cCR 20 F 65 T3N+ Pembro cCR 10 F 81 T3N0 Dorstali cPR 21 F 39 T4N+ Dorstali cSD 11 F 32 T2N+ Pembro cCR