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e20520 Background: Cancer and respiratory failure (RF) are amongst leading causes of mortality in adults. This study investigates national trends in age-adjusted mortality rates (AAMRs) for cancer and RF in the United States from 1999 to 2023, focusing on disparities by gender, race, region, and rural-urban residence to inform public health strategies. Methods: This descriptive study analyzed data from the CDC WONDER database, of adults aged 25 and older. Mortality data were identified using ICD-10 codes C00–C97 (cancer) and J96 (RF). AAMRs per 100,000 population were calculated and stratified by gender, race/ethnicity, census region, urban-rural classification, and state. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05. Results: From 1999 to 2023, total deaths of 1,263,368 attributed to cancer and RF (682,141 men, 581,227 women). AAMRs declined from 1999 to 2004 (APC = -1.5, 95% CI: -4.0 to -0.4), stabilized from 2004 to 2012 (APC = 0.8, 95% CI: 0.1 to 2.4), and increased from 2012 to 2023 (APC = 3.2, 95% CI: 2.9 to 3.8). Men experienced a greater initial decline (APC = -2.1, 1999–2004) but significant increases thereafter (APC = 3.0, 2012–2023), while women showed a slower decline followed by sharper increases (APC = 3.5, 2013–2023). Non-Hispanic Black populations initially declined (APC = -1.7, 1999–2003) but later increased significantly (APC = 3.0, 2014–2020). Hispanic/Latino populations declined (APC = -1.2, 1999–2009) before rising sharply (APC = 3.1, 2009–2020). American Indian or Alaska Native populations showed consistent increases (APC = 1.7, 1999–2020). Urban areas experienced initial declines (APC = -1.7, 1999–2004), followed by increases (APC = 2.4, 2011–2020). Non-metropolitan areas exhibited steeper increases (APC = 4.6, 2014–2020). Regionally, the West recorded the highest AAMR (24.0), followed by the Northeast (23.6), South (20.9), and Midwest (18.0). Mississippi had the highest state-level AAMR (36.3), while Wisconsin had the lowest (10.0). States in the top 90th percentile included Mississippi, Arkansas, and California, while Wisconsin, Minnesota, and Oregon were among the lowest. Conclusions: Cancer and RF mortality declined initially but have significantly increased in recent years. Disparities persist across gender, racial, and regional groups, underscoring the need for focused public health efforts and equitable resource distribution to address these trends.

e19531 Background: Effective treatment and elimination of clonal plasma cells (PC) in multiple myeloma (MM) are typically associated with recovery of polyclonal (normal) plasma cells (PPC). Studies suggest that robust PPC recovery is associated with better outcomes. However, it is unclear if this remains valid in the context of monoclonal antibodies, such as Daratumumab, that selectively target plasma cells, and in turn, may adversely impact PPC recovery. Methods: We identified patients with MM who underwent MRD testing using Euroflow method at 6-12 months after treatment initiation. Eight patients had disease progression prior to MRD testing and were excluded from further analysis. PPC was quantitated by the proportion of total events acquired during flow examination. Patients were considered MRD-negative if they had <1 clonal PCs in 10 5 cells, as detected in the marrow. We first examined the impact of initial therapy (Daratumumab vs. non-Daratumumab based regimens) and MRD status on PPC recovery. Subsequently, we analyzed impact of PPC recovery on patient outcomes in terms of progression-free survival (PFS) and overall survival (OS). Results: We identified 572 patients who had MRD testing by flow at a median of 9 months (range 6-12) after treatment initiation. The median age was 63 years, 58% were male. Daratumumab was part of initial therapy in 17% of patients; the most common induction therapies were PI-IMiD triplets (73%), and dara-PI-IMiD quads (15%). In our cohort, 74% of patients were MRD-negative. In our practice, only samples with no monotypic PCs identified on initial low-sensitivity flow proceed to MRD testing, hence, the proportion of MRD-negative patients appears higher in our study than previously reported. Median PPC was 0.02% and was similar between MRD-negative and -positive patients. We found the median PPC was significantly low in patients who received Daratumumab compared to the non-Daratumumab treated cohort (0.011% vs. 0.023%; p<0.01). There was a trend towards lower PFS and OS among the lowest PPC quartile group compared to the upper 3 quartiles, although this was not significant (p=0.07 for PFS and OS, Wilcoxon). This trend was more evident among patients who did not receive Daratumumab. Conclusions: Our study demonstrates negative impact of anti-CD38 therapy with Daratumumab on recovery of PPCs after initial treatment, consistent with the persistent hypogammaglobulinemia seen in clinical practice among these patients. However, unlike the observation with the non-Daratumumab treated cohort, the low proportion of PPCs does not significantly impact patient outcomes among patients who received Daratumumab.

3553 Background: Vilastobart (XTX101) is tumor-activated, high affinity, Fc-enhanced aCTLA-4 designed to focus activity toward the tumor and minimize systemic adverse events. Fc-enhancement augments FcγR co-engagement on antigen presenting cells and has been linked with efficacy of aCTLA-4 combinations in patients (pts) with microsatellite stable (MSS) colorectal cancer (CRC) and other tumors [Fakih ASCO GI 2025]. Vilastobart was generally well-tolerated and demonstrated evidence of anti-tumor activity in pts with immunologically “cold” advanced solid tumors, both as a monotherapy and in combination with atezolizumab [Davar SITC 2024]. Methods: Phase 2 of the NCT04896697 study evaluated the initial recommended Phase 2 dose of vilastobart 100 mg Q6W in combination with atezolizumab 1200 mg Q3W in pts with MSS CRC who had at least 1 prior chemotherapy regimen in the metastatic setting, excluding pts with prior immune checkpoint inhibitors. Pts with (LM) and without liver metastasis (NLM) were eligible. Tumor biopsies were obtained before and during treatment for translational analyses. Results: As of January 13, 2025, 40 pts were dosed in Phase 2. Median age was 55 (25-82) and 70% of pts had 3 or more prior lines of therapy. Of the 24 enrolled NLM pts, 11 were response-evaluable with an available on-treatment scan as of the data cut. In these 11 pts, two confirmed and one unconfirmed partial response (PR) were reported, all accompanied by significant decreases in ctDNA and serum tumor marker CEA and with each pt ongoing on therapy, for a preliminary ORR of 27%. One additional pt (with peritoneal metastasis) had a 24% reduction in target lesions (first scan) and was ongoing on therapy. Of the 16 enrolled LM pts, 7 were response evaluable, with one stable disease and another pt reporting a mixed response with significant serum tumor marker reductions, both ongoing on therapy. Of note, one LM pt in Phase 1C dose escalation treated with vilastobart (150 mg Q6W) combination had a confirmed PR with LM resolution. Six pts (15%) reported G3+ treatment-related adverse events (TRAEs), with two G4 laboratory TRAEs and no G5 TRAEs. Only three pts discontinued therapy for TRAEs. TRAEs occurring in ≥10% (all grade) or ≥5% (G3) of pts are summarized in the Table. Conclusions: The combination of vilastobart, a novel tumor-activated, Fc-enhanced a-CTLA-4, and atezolizumab demonstrated initial evidence of anti-tumor activity in late line, metastatic MSS CRC where immune checkpoint blockade has historically been relatively ineffective. Vilastobart was observed to have a differentiated safety profile distinct from systemically active a-CTLA-4, consistent with tumor-selective activation. Clinical trial information: NCT04896697 . AE term All Graden (%) Grade 3n (%) Fatigue 12 (30%) 0 Diarrhea 8 (20%) 0 Infusion related reactions 5 (13%) 0 Pyrexia 4 (10%) 0 ALT increased 4 (10%) 0 AST increased 4 (10%) 1 (3%) Colitis 2 (5%) 2 (5%)

11507 Background: Advanced uterine leiomyosarcoma (uLMS) is an aggressive malignancy with poor prognosis. Standard-of-care treatments, including trabectedin (Tb) or pazopanib (P), provide median progression-free survival (PFS) of 3-4 months (mo) and objective response rates (ORR) of ~11%. Homologous recombination deficiency (HRD) in a subset of uLMS supports the use of PARP inhibitors combined with DNA-damaging agents. Preclinical studies demonstrated synergistic activity of olaparib and temozolomide (T+O), and a prior single-arm Phase II study of T+O showed promising efficacy independent of an established biomarker, warranting further investigation in a randomized setting. Methods: Alliance A092104 is a Phase II/III trial evaluating olaparib (200 mg BID) plus temozolomide (75 mg/m² daily, days 1-7, every 21 days) versus investigator’s choice of Tb or P in patients (pts) with advanced uLMS who progressed on ≥2 prior systemic therapies. Stratification factors included ECOG (0-1 vs. 2) and prior lines (2 vs. ≥3). The Phase II (Phase III) primary endpoint was PFS (OS), with a planned suspension of accrual at the end of Phase II. A total of 70 evaluable pts (58 PFS events) were needed to detect an improvement in PFS from 4 vs. 8 mo with power of 90% and 1-sided type I error of 10%, with futility assessed after 29 PFS events. Upon meeting the Phase II futility threshold for PFS, the trial was permanently closed. Data were released from the data and safety monitoring board. Pts continue to be followed for outcomes. Results: 74 pts enrolled (Arm 1: T+O, n = 37; Arm 2: investigator’s choice, n = 37 (Tb, 18; P, 13; 6 pts did not start treatment). The arms were balanced for baseline demographics except race, with the T+O arm having a higher proportion of black/African American (29.7% vs. 16.2%). 21 pts remain on treatment. Hematologic adverse events (AEs) were more frequent in the T+O arm, with Grade 4 neutropenia (19.5%) and thrombocytopenia (8.3%) both managed by dose reductions. Non-hematologic Grade 3 AEs were higher in the investigator’s choice arm (45.2% vs. 13.9%). No Grade 5 AEs were reported. In the first 70 pts, with a median follow-up of 5.9 mo, and 39 total PFS events, the median PFS was 3.2 mo (95% CI: 2.0-NE) for T+O versus 5.6 mo (95% CI: 2.8-NE) for investigator’s choice (HR = 1.00; 95% CI: 0.60-2.17; 1-sided stratified log rank p = 0.50). Within Arm 2, the median PFS for Tb and P were respectively 5.6 (95% CI: 3.1-NE) and 3.8 (95% CI: 1.5-NE) mo. 3 pts in the T+0 arm and 1 patient in the investigator’s choice arm (Tb) had a confirmed partial response. Conclusions: The trial did not meet its primary endpoint of PFS in Phase II. This suggests that a biomarker may be needed before there is further exploration of PARP inhibitor-based regimens in uLMS. Overall survival and analysis of tissue-based biomarkers will be presented. Clinical trial information: NCT05432791 .

TPS1143 Background: Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have revolutionized the treatment of patients (pts) with germline BRCA1/2 (gBRCA)-associated HER2-negative BC. However, resistance eventually occurs in almost all pts. Tumor-associated macrophages (TAMs), a key component of the BC tumor microenvironment, are highly immunosuppressive and associated with poor clinical outcomes. In preclinical immunocompetent models of BRCA-associated BC, PARP inhibition induces suppressive CSF-1R+ TAMs, contributing to resistance, so that combining anti-CSF-1R therapy with PARPi significantly enhances progression free survival (PFS) compared to PARPi monotherapy (190d vs 92d). Axatilimab (SNDX-6352; Ab969.g2), a humanized IgG4 monoclonal antibody targeting CSF-1R, reduces TAMs, potentially slowing tumor growth and enhancing anti-tumor immunity. In the Phase I SNDX-6352-0502 study for advanced solid tumors, axatilimab showed tolerability at the highest dose (6 mg/kg), with biomarker modulation observed at doses as low as 1 mg/kg. Axatilimab is FDA-approved for chronic graft-versus-host disease (cGVHD). Methods: AXALAP (NCT06488378) is a non-randomized open-label, proof-of-concept phase 1 study designed to evaluate axatilimab 1mg/kg or 3mg/kg every 2 weeks in combination with olaparib 300 mg twice daily in pts with somatic or germline BRCA1/2 - and PALB2 -associated HER2-negative metastatic BC. Patients must be PARPi naïve, or have not progressed on prior PARPi, and have received up to 2 prior lines of chemotherapy for metastatic disease. Pts will receive a two-week lead-in of olaparib monotherapy, followed by combined olaparib and axatilimab. Pts will undergo mandatory tumor biopsies pre-treatment, after the 2-week olaparib lead-in, and after 2 cycles of olaparib/axatilimab, with an optional biopsy at time-of-progression. Primary objectives are to establish the maximum tolerated dose (MTD) and recommended phase 2 dose and to assess the safety and tolerability of axatilimab and olaparib. Secondary objectives include assessment of changes in CSF-1R+ CD163+ macrophage levels after olaparib monotherapy and after 2 cycles of combination treatment at the MTD; to determine the objective response rate and the median PFS of the combination per RECIST 1.1 criteria. The MTD will be determined by Bayesian Optimal Interval (BOIN) design. Pts will be treated in cohorts of 3 with a maximum of 10 at each dose. If the MTD is identified as 3mg/kg, we will complete enrollment of 10 pts at 1 mg/kg to assess biological effectiveness and clinical efficacy of the lower dose. We expect to treat up to 20 pts, who will receive study treatment until development of unacceptable toxicity or disease progression. Enrollment began on 5/2024 at Dana-Farber Cancer Institute and the trial will also open at Beth Israel Deaconess Medical Center and Mayo Clinic-Rochester. Clinical trial information: NCT03604692 .

TPS1138 Background: The SV-BR-1-GM breast cancer cell line activates anti-tumor immunity by expressing tumor associated antigens and secreting GM-CSF which enhances dendritic cell activation and promotes adaptive (T-cell mediated) and innate (dendritic and NK cell) immune responses. The cells are also engineered to optimize immune recognition through pt specific HLA antigen matching. SV-BR-1-GM acts through direct antigen presentation and CD4+ T-cell activation and, when combined w/ checkpoint inhibitors (CPIs), has demonstrated clinical benefit in 54 heavily pretreated metastatic breast cancer (MBC) pts. In pts w/ disease progression following CPI therapy, similar or improved progression free survival (PFS) compared to their prior treatment regimen. Disease control following antibody drug conjugates was observed in 40%of pts. Clinical benefit was seen in 5 out of 8 pts w/ untreated intracranial metastases. CD8+ Immuno-PET imaging suggests systemic activation, w/ increased CD8+ tumor infiltrating lymphocytes at both primary and metastatic tumor sites, as well as lymphoid organs. Optimized sequencing of CPI w/ SV-BR-1-GM and its latest phase 3 formulation have shown enhanced clinical outcomes, including improved overall survival (OS) (median 13.4 mos), PFS (3.6 mos), and clinical benefit rate (CBR; 61%).These findings have informed refinements to the ongoing pivotal, registration enabling Phase 3 trial, designed to optimize pt selection and treatment sequencing strategies. Methods: This ongoing multicenter, randomized, open label Phase 3 trial evaluates Bria-IMT + CPI vs. Treatment of Physician’s Choice (TPC) in MBC pts lacking approved curative therapies. Pts are randomized 1:1:1 to Bria-IMT + CPI, TPC, or Bria-IMT monotherapy (discontinued after 150 enrollments to prioritize combination arms). The Bria-IMT regimen consists of: Day -2: Cyclophosphamide 300 mg/m², Day 0: 20M irradiated SV-BR-1-GM cells, Day 2/3: 0.1 mcg pegylated α interferon at each inoculation site. CPI infusion is administered Day -3 to 3. Cycles q3w. TPC regimens follow site specific SOC. Imaging q6w (first 2 cycles), then q8w. Eligibility includes all MBC subtypes, including CNS mets, and permits prior CPI therapy ( >21 days pre-treatment). There will be 100 sites across the U.S., Canada, and ex-North America w/ an enrollment target of 404. The trial is currently active at 59 sites with 217 sub investigators. To date, 67 pts screened: 46 randomized (median age 56 yrs [34–83], median 6 [2–13] prior lines of therapy. The primary endpoint is OS, with an interim analysis at 144 events targeting a hazard ratio of 0.6. Secondary endpoints: PFS, overall response rate, CBR, CNS event free survival, and TWiST. Safety analyses ongoing; pt reported outcomes assess subjective treatment impact. Clinical trial information: NCT03328026 .

6073 Background: Laryngeal Squamous Cell Carcinoma (LaSCC) has varying outcomes based on the stage of cancer patients present with. Currently, a high proportion of patients are diagnosed with advanced-stage LaSCC complicating the treatment landscape and over-treating low risk patients. Risk stratification of LaSCC can help tailor treatment plans. Numerous studies have identified spatial architecture of tumor-infiltrating lymphocytes (TILs) as a prognostic biomarker in oral cavity and oropharyngeal SCC. In this work, we evaluate the prognostic value of an artificial intelligence (AI)-leveraged approach that characterizes the spatial architecture of TILs on digitized hematoxylin and eosin (H&E)-stained slides from patients with LaSCC. Methods: H&E slides from 192 patients with LaSCC were collected from Baylor Medical Center. This dataset was randomly divided into two equal cohorts, A and B. The slides were digitized as whole slide images at 40x magnification. The nuclei of all cells were automatically segmented using a deep-learning model (Hover-Net). Each nucleus was then classified as TIL or non-TIL based on morphological features. TILs and non-TILs were clustered based on proximity, and features related to the density and spatial distribution were extracted. The top features, determined by the least absolute shrinkage and selection operator, were used to train a Cox Proportional Hazards regression model that assigned a risk score for recurrence of cancer to each patient in cohort A. For validation, the model was applied to patients in cohort B. The 25 th percentile training risk score was used as a cutoff for classifying patients as high or low risk. The performance of the model in prognosticating loco-regional recurrence (LRR) was evaluated using survival analysis. Results: Patients in Cohort B identified as “high risk” by the model based on spatial organization of TILs had a significantly shorter survival time. Univariate survival analysis showed this model was prognostic for DFS with a hazard ratio of 2.57 (95% Confidence Interval: 1.12-5.89, p-value=0.048), meaning that patients classified as “high risk” are approximately 2.5 times more likely to develop LLR. Conclusions: We used computational pathology to characterize the architecture of TILs and develop a model to predict risk of LLR in LaSCC. With additional validation, this approach can be used to assist clinicians with making clinical decisions. Multivariate analysis. Variable Reference vs Comparison Pr(>|z|) HR (95% CI) Race Black vs Caucasian 0.93 0.92 (0.40 - 2.31) N N0 vs N+ 0.67 1.80 (0.12 - 26.06) T 1-2 vs 3-4 0.83 1.28 (0.13 - 12.38) Chemo Yes vs No 0.38 3.49 (0.21 - 56.90) Tobacco Yes vs No 0.26 2.08 (0.58 - 7.47) Alcohol Yes vs No 0.43 1.53 (0.54 - 4.35) TIL Architecture Risk High vs Low 0.03 * 0.26 (0.08 - 0.89)

6057 Background: The incidence rate of human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) has persistently increased over the past decade and is anticipated to rise further over the next decade. Cost effective, accurate, and less invasive screening options for HPV(+)OPSCC have remained stagnant leading to the interrogation of circulating tumor DNA in liquid biopsies such as plasma. We hypothesized that candidate methylated DNA markers (MDMs), previously described by our group, would be present in the plasma of patients with HPV(+)OPSCC and absent in controls. Methods: HPV(+)OPSCC cases were enrolled from a high-volume referral practice. Cancer-free control patients were identified from the surrounding 7-county catchment area and frequency matched to cases by age and alcohol use. cfDNA was extracted from 4 mL of plasma and bisulfite converted prior to Target Enrichment Long-probe Quantitative Amplified Signal assays for 15 MDMs. Strand counts for individual MDMs were normalized to a methylated genomic reference marker. An MDM score was derived via random forest modeling of the 15 MDMs. Area under the receiver operator characteristic curve (AUC) for discriminating cases from controls was evaluated for individual markers and for the MDM score. The sensitivity of the MDM score at 95% specificity was also evaluated. Results: The study consisted of 96 HPV(+)OPSCC and 100 cancer-free controls. The study population was predominately white (95%) with a median age of 61 yrs (IQR: 52-69 yrs). Eighty-nine percent of the cases were male with cancers affecting either the tonsil in 50 (52%) or base of the tongue in 46 (48%) patients; by design 50% of controls were male. Stage I:II:III:IV disease was present in 66%:22%:9%:3% of the cases. The median (IQR) AUC across the 15 MDMs was 0.83 (0.82-0.85) overall: 0.78 (0.77-0.83) for stage I disease and 0.92 (0.91-0.93) for stage II-IV disease. The MDM score for the combined panel of 15 MDMs achieved a cross-validated AUC of 0.93 (CI: 0.89-0.97) overall: 0.90 (CI: 0.84-0.96) for stage I disease and 0.98 (CI: 0.97-1.00) for stage II-IV disease. At 95% specificity, the cross-validated sensitivity of the MDM score for HPV(+)OPSCC was 80% (CI: 71-87%) overall: 73% (CI: 60-83%) for stage I disease and 94% (CI: 78-99%) for stage II-IV disease. Conclusions: We validated a set of previously discovered MDM markers in HPV(+)OPSCC in a robust case control cohort using plasma. The MDMs were detected in both early and late-stage disease. Additional prospective studies in larger intended use cohorts are needed to validate our results for clinical use.

1114 Background: While treatment and management of TNBC has improved, there is a need for novel prognostic biomarkers to better inform outcomes and guide therapeutic options. ILF2 is a poorly characterized protein with pleiotropic functions that is highly expressed in TNBC. Here we evaluated the associations of ILF2 with 1) genomic and transcriptomic data, 2) tumor microenvironment (TME), and 3) clinical outcomes in TNBC. Methods: 15,544 breast cancer (BC) samples, including 3,038 TNBC, were tested by NGS (592, NextSeq; WES, NovaSeq) and WTS (NovaSeq; Caris Life Sciences, Phoenix, AZ). ILF2 -high (H) and ILF2 -low(L) TNBC were defined by respective quartiles. Immune cell fractions were estimated by WTS deconvolution (Quantiseq). Real world overall survival (OS) was obtained from insurance claims and calculated from tissue collection to last contact using Kaplan-Meier estimates. Statistical significance was determined by chi-square, Fisher’s exact, and Mann-Whitney U test with p-values adjustments (q < .05). Results: ILF2 expression (median Log2(TPM+1) was higher (all q < .05) in key subgroups: ductal compared to lobular carcinoma (6.4 vs 6.0); primary compared to metastatic BC (6.4 vs 6.3); African American compared to White (6.4 vs 6.3); basal compared to luminal A, luminal B, HER2 PAM50 subtypes (6.9 vs 5.8, 6.3, 6.3); and TNBC compared to HR+HER2+, HR-HER2+, HR+HER2- subtypes (6.7 vs 6.3, 6.4, 6.2). Biopsied tissues from primary TNBC (pTNBC) and metastatic TNBC (mTNBC) patients were stratified into ILF2- H and ILF2- L groups. In both mTNBC and pTNBC, ILF2- H groups had 1) higher percentage of young patients (age < 50) (pTNBC: 35.5% vs 19.8%; mTNBC: 28.1% vs 17.3%; all q < .05); 2) higher mutation frequency of TP53 (pTNBC: 94.5% vs 79.6%; mTNBC: 92.4% vs 74.4%), but lower frequencies for PIK3CA ( pTNBC: 5.1% vs 23.4% , mTNBC: 8.8% vs 27.4%), CDH1 ( pTNBC: 0.8% vs 6.1%; mTNBC: 2.8% vs 12.2%; all q < .05); 3) higher infiltration of NK cells (pTNBC: 3% vs 2.6%; mTNBC: 2.8% vs 2.6%), but lower infiltration of M2 Mφ (pTNBC: 2.5% vs 3.3%; mTNBC: 2.6% vs 3.2%) and Tregs (pTNBC: 1.5% vs 1.9%; mTNBC: 1.4% vs 1.7%; all q < .05); 4) higher expression levels of immune checkpoint ( CD274, PDCD1LG2, CTLA4, LAG3, HAVCR2, FOXP3, IDO1, CD276 , FC: 1.2-3.1; all q < .05), stem cell genes (C D44, NANOG, POU5F1, KLF4, ALDH1A1 , FC: 1.4-2.4; all q < .05), and drug efflux genes ( ABCC3, ABCC11, ABCC2, ABCB1, ABCG2, ABCC1 , FC: 1.1-4.5; all q < .05) compared to ILF2- L group. In pTNBC, ILF2- H had significantly shorter OS vs ILF2- L group (22.3 vs 28.9 months, HR 1.2 [95% CI 1-1.5], p = .03), but no significant differences were observed between mTNBC ILF2 groups (HR 1.1 [95% CI 0.93-1.3], p = .2). Conclusions: ILF2 -H TNBC patients showed differential genomic and transcriptomic alterations that relate to therapy resistance, immune suppressive TME, and shorter OS. Further studies are warranted to validate the effects of ILF2 upregulation on therapeutic efficacy.