Citations

e16435 Background: Peritoneal metastasis in pancreatic ductal adenocarcinoma (PDAC) is historically associated with a dismal prognosis and limited response to systemic therapy alone. The role of locoregional therapy remains controversial. This study evaluated the survival impact and safety of HIPEC, with or without cytoreductive surgery (CRS), compared to standard-of-care systemic therapy in patients with peritoneal metastatic PDAC. Methods: We conducted a comparative analysis of 130 patients with peritoneal metastatic PDAC, comprising a study cohort treated with HIPEC (n = 33) and a control group treated with systemic chemotherapy alone (Non-HIPEC, n = 97). HIPEC patients received induction chemotherapy (predominantly FOLFIRINOX) followed by HIPEC ± CRS. Co-primary endpoints included 12 months survival, and 6 months progression free survival (PFS). Secondary endpoints evaluated Overall Survival (OS ), safety of CRS, and impact of germline mutation status on survival. Study was approved under IRB protocol 25-008762. Results: The 12-month OS rate was significantly higher in the HIPEC group compared to the chemotherapy-only control group (100% vs. 52.6%, P < 0.001). The 6-month PFS rate in the HIPEC group was 63.0% vs. 47.94 in-only control group (P < 0.001). For secondary endpoints, the HIPEC group demonstrated a significantly longer median OS of 33.0 months vs. 17.0 months for controls (P < 0.001). Within the HIPEC cohort, the addition of CRS (n = 25) significantly improved outcomes compared to HIPEC alone (n = 8): median OS improved from 21.5 to 36.0 months (P = 0.03). Germline testing was performed in 61% of HIPEC patients and 48% of controls, identifying pathogenic mutations in 25% and 17%, respectively. Identified pathogenic mutations in both groups included ATM (n = 4), MUTYH (n = 2), BRCA2 (n = 1), CHEK2 (n = 1), PALB2 (n = 1), and KIT (n = 1). In the control group, specific mutations drove divergent outcomes; ATM median OS: 23.5 months vs. MUTYH : 8.0 months (P = 0.04). Conversely, in the HIPEC+CRS cohort, survival was excellent regardless of genetic profile: mutation carriers achieved a median OS of 33.0 months compared to 31.0 months in wild-type patients (P = 0.85). Despite a 34.8% postoperative complication rate in the HIPEC group, there was no perioperative mortality. Conclusions: In selected patients with peritoneal metastatic PDAC, HIPEC provides a substantial survival advantage over systemic therapy alone, achieving a 100% 12-month survival rate and more than doubling the median overall survival. Importantly, germline mutation status did not preclude survival benefit, with mutation carriers deriving equal efficacy from the multimodal approach. These findings support HIPEC+CRS as a highly effective strategy that may overcome adverse biologic drivers.

9021 Background: An escape room is a team-based activity in which participants collaborate to solve puzzles within a fixed time limit and escape. Prior studies demonstrate high learner satisfaction and improved teamwork and communication with medical education escape rooms. To date, no published reports describe an escape room designed specifically for hematology/oncology (hem/onc) fellows. As part of Hem/Onc Curriculum, we designed and implemented a hem/onc-focused escape room and evaluated learner satisfaction and perceived learning impact. Methods: The escape room was designed using evidence-based learning science principles (Table 1). Teams worked to solve sequential puzzles, centered on a patient case, addressing key hem/onc concepts, including transfusion medicine, peripheral blood smears, lymphoma classification, and coagulation disorders. Each solved puzzle revealed additional patient laboratory and pathology data. Successful completion required teams to diagnose the patient and select appropriate treatment. Following the activity, teams participated in a facilitator-led debrief focused on team dynamics, communication, and problem solving. Teams observed each other and shared feedback. A larger group debrief co-led by chief fellows and faculty reviewed learning objectives and key takeaways. Learner outcomes were assessed using a post-activity survey evaluating satisfaction, engagement, and impact on learning. Results: Eighteen learners participated, including 14 hem/onc fellows, 1 APP hem/onc fellow, and 3 internal medicine residents. Three of four teams escaped within 1 hour (mean completion time, 52 minutes). All participants provided positive verbal feedback. Fifteen learners completed the post-activity survey, and all respondents reported satisfaction with the activity and would recommend it for future fellows. One-word descriptors included “engaging,” “fun,” and “challenging.” Most respondents (93.3%) agreed that the activity reinforced key hem/onc concepts and improved confidence in clinical problem-solving. All learners felt the activity supported learning, and 93.3% reported that collaboration enhanced the learning experience. Participants identified team-based problem solving, clinical application, and interactive puzzles as the most effective components. Conclusions: A hem/onc escape room resulted in high learner satisfaction and reinforced hem/onc knowledge and clinical problem-solving. This feasible, fun, and innovative activity complements traditional fellowship education by leveraging adult learning principles through gamified, team-based learning and should be incorporated into training programs’ curriculum. Learning science principles applied in a hem/onc escape room. Active Learning Belonging Contrasting Cases Debriefing Deliberate Practice Elaboration Generation Listening and Sharing Reward Worked Examples

Abstract Background: Early-onset gastrointestinal (GI) cancers are increasing globally, yet the genomic basis for age-related differences across multiple tumor types remains poorly defined. We leveraged AACR Project GENIE v18.0 (N≈34,000 GI tumors) to characterize molecular distinctions by age in colorectal, pancreatic, small bowel, and anal cancers with sufficient early-onset representation. Methods: Clinical and genomic data were extracted and tumors classified into early-onset (&lt;50 years) and late-onset (≥50 years). Mutation frequencies were compared by cancer type and age group, focusing on recurrent drivers, DNA repair, Wnt signaling, RAS/MAPK, chromatin remodeling genes, and targetable alterations. Results: Early-onset colorectal cancer (N=5,724) showed increased Wnt/β-catenin pathway alterations: APC (+4.9%), TCF7L2 (+4.1%), and TP53 (+5.0%), while late-onset tumors (N=15,807) were enriched for BRAF (−5.4%), RNF43 (−1.9%), and GNAS (−1.1%), indicating divergent tumorigenic pathways. Early-onset pancreatic cancer (N=890) exhibited significantly lower frequencies of canonical drivers—KRAS (−24.7%), TP53 (−15.6%), CDKN2A (−6.9%), SMAD4 (−6.0%)—with enrichment of MEN1 (+3.5%), TSC2 (+3.0%), ATRX (+2.0%), DAXX (+1.9%), and CTNNB1 (+2.4%), consistent with fusion-driven, hereditary, and chromatin remodeling biology. Small bowel cancer (N=99) in early-onset patients demonstrated enrichment in DNA damage response and MAPK/RAS genes including BRCA2 (+7.2%), NF1 (+7.4%), FBXW7 (+8.8%), FLT4 (+6.5%), ARAF (+6.4%), and ALK (+5.1%), whereas late-onset tumors (N=538) were enriched for KDR (−5.1%) and MGA (−5.2%). Early-onset anal cancer (N=62) showed elevated MGA (+7.8%), WHSC1/NSD2 (+6.9%), PBRM1 (+6.2%), FANCA (+5.2%), ERCC5 (+6.2%), and MSH6 (+5.9%), highlighting chromatin remodeling and DNA repair pathways potentially related to HPV biology; late-onset tumors (N=464) had enrichment in ATM (−5.6%), PTEN (−5.5%), STK11 (−5.2%), APC (−5.2%), and KMT2C (−5.0%), reflecting age-associated genomic instability. Conclusions: This pan-GI age-stratified analysis reveals distinctive oncogenic programs in early-onset GI cancers characterized by Wnt/TP53-driven colorectal, fusion- and chromatin remodeling-driven pancreatic, DNA damage response/MAPK-driven small bowel, and chromatin-immune DDR signatures in anal cancers. These findings underscore the need for age-tailored precision oncology and support routine genomic profiling in early-onset GI malignancies to identify targetable alterations enriched in younger patients. Citation: AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine Through an International Consortium. Cancer Discov. 2017;7(8):818-831. (Data: GENIE Release 18.0-public)Acknowledgement: AACR and Project GENIE registry Citation Format: Ahmed Abdelhakeem, Nency Ganatra, Dina Elantably, Tayo Adeoye, Nayef H. Abdel-Razeq, Mosalem M. Osama, Hani M. Babiker. Distinct age associated genomic landscapes in colorectal, pancreatic, small bowel, and anal cancers: A pan gastrointestinal analysis of 34,000 tumors from AACR Project GENIE v18.0 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4105.

Abstract Background: PARP inhibitors are restricted to a subset of BRCA-associated cancers, but homologous recombination repair (HRR) deficiency signifies a broader genomic vulnerability that may extend therapeutic opportunities across diverse malignancies. We utilized AACR Project GENIE v18.0-public to define the pan-cancer prevalence of HRR gene alterations. Methods: Somatic mutation and clinical sample data from GENIE v18.0-public were analyzed. HRR genes included BRCA1, BRCA2, ATM, CHEK2, PALB2, RAD51B/C/D, RAD51L1, BARD1, BRIP1, and core FANC genes. HRR alteration rates were calculated by tumor type using unique samples; only de-identified aggregate results are reported. Results: Among 101,240 tumors, HRR gene alterations were frequent in multiple non-BRCA-associated cancers. Highest rates were seen in sialoblastoma (100%), large cell medulloblastoma (50%), malignant glomus tumor (50%), lung cancer (46.0%), infantile fibrosarcoma (42.9%), liver (40%), kidney (40%), non-melanoma skin (36.9%), colorectal (36.6%), melanocytoma (34.2%), biliary tract (33.3%), bladder (31.5%), and ovarian/fallopian tube (30.2%). Notably, lung, bladder, hepatobiliary, renal, gastrointestinal, and some sarcoma subtypes showed HRR mutation prevalence equal or higher than current PARP indications, yet lack FDA approval. Conclusions: HRR alterations are widespread across solid tumors, often surpassing rates in cancers eligible for PARP treatment. These findings support expanding tumor-agnostic HRR genomic testing beyond BRCA-linked malignancies and warrant prospective trials of PARP inhibitors in HRR-enriched tumor types such as lung, bladder, hepatobiliary, renal, gastrointestinal, and pediatric/rare cancers. Impact: Large-scale genomic profiling from AACR Project GENIE demonstrates that HRR gene alterations are common across diverse solid tumors, with prevalence in multiple cancer types surpassing those currently eligible for PARP inhibitor therapy. These findings support broad implementation of HRR genomic testing in routine molecular diagnostics and provide a rationale for expanding PARP inhibitor use beyond BRCA-associated malignancies. The data justify prospective tumor-agnostic clinical trials of PARP inhibitors in HRR-enriched cancers such as lung, bladder, hepatobiliary, renal, gastrointestinal, and select pediatric and rare tumors; this could transform therapeutic decision-making and accelerate development of synthetic lethality-based targeted therapies Citation: AACR Project GENIE Consortium. Cancer Discov. 2017;7(8):818-831 Acknowledgement: AACR and Project GENIE Citation Format: Ahmed Abdelhakeem, Nency Ganatra, Dina Elantably, Tayo Adeoye, Nayef H. Abdel-Razeq, Osama M. Mosalem, Hani M. Babiker. Pan cancer enrichment of homologous recombination repair (HRR) gene alterations in 101,240 tumor samples from AACR Project GENIE: Implications for tumor-agnostic PARP inhibitor expansion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4106.

741 Background: IP strategies directly target the peritoneal compartment in PDAC, where systemic chemotherapy alone demonstrates poor efficacy. Approaches include HIPEC, normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX) given with systemic therapy, and PIPAC. This systematic review synthesizes evidence on feasibility, perioperative safety, and clinical outcomes of IP therapy in PDAC. Methods: We conducted a systematic search in PubMed, Embase, Scopus, and Cochrane databases for studies published through August 2025. Eligible studies included prospective or retrospective studies evaluating HIPEC, NIPEC/IP-PTX, or PIPAC with extractable safety or oncologic outcomes. Outcomes included feasibility, 30-day mortality, perioperative complications, locoregional recurrence (LRR) in the adjuvant setting, overall survival (OS) from peritoneal metastasis (PM) diagnosis or first IP therapy, conversion-to-resection, and histologic/radiologic response. Results: Sixteen studies met criteria, including 7 on HIPEC, 5 on NIPEC/IP-PTX, and 4 on PIPAC. In the adjuvant setting, 2 HIPEC studies demonstrated high feasibility (>85%), 0–5% 30-day mortality, and complication rates comparable to pancreatectomy. A randomized trial reported significantly lower LRR with adjuvant gemcitabine HIPEC. Median OS in treated arms was ~17–18 months, with 1-year OS ~63%. In the cytoreductive surgery (CRS) plus HIPEC setting for isolated peritoneal metastases, patients achieved CC-0/1 cytoreduction in most cases, with median OS ~24–41 months and 1-, 2-, and 3-year OS ranging 60–91%, 33–66%, and 39–59%, respectively. Thirty-day mortality was 0–4.3%, and major morbidity 20–43%. For NIPEC/IP-PTX, multicenter and single-institution cohorts consistently reported median OS ~14–16 months, 1-year OS ~60%, and conversion-to-resection rates of 17–24%. Ascites control and feasibility were reproducible, and device-related adverse events were generally manageable. PIPAC programs established oxaliplatin at 120 mg/m² as the recommended dose, with ~50–60% histologic regression by PRGS and disease stabilization in 50–60% after 1–2 cycles. Median OS in PDAC subsets was ~9–13 months, with low major toxicity, though early discontinuation was frequent in progressive disease. Conclusions: Intraperitoneal therapies for PDAC are feasible and show promising biologic and clinical signals. Adjuvant HIPEC reduces locoregional recurrence without excess mortality; CRS plus HIPEC can achieve multi-year survival in selected patients with isolated PM metastases; NIPEC/IP-PTX offers reproducible survival and conversion-to-resection; and PIPAC provides histologic regression with acceptable safety.

117 Background: Oxaliplatin remains a cornerstone of colorectal cancer (CRC) chemotherapy but is frequently complicated by chemotherapy-associated liver injury (CALI). This manifests as sinusoidal obstruction syndrome (SOS), nodular regenerative hyperplasia (NRH), or porto-sinusoidal vascular disorder (PSVD). These microvascular changes lead to portal hypertension (PH), splenomegaly, and thrombocytopenia, interrupting chemotherapy delivery and compromising survivorship. Despite increasing recognition, the incidence, spectrum, and management of oxaliplatin-induced portal hypertension (OIPH) remain undefined. Methods: We systematically reviewed PubMed, Embase, and Cochrane through August 2025 for prospective and retrospective cohorts of oxaliplatin-treated CRC patients reporting OIPH incidence, pathology, radiology, or interventional management. Case reports were excluded. Outcomes included incidence, latency, complications, misdiagnosis, and interventions such as bevacizumab and partial splenic embolization (PSE). Results: Eight studies including 730 patients were analyzed. OIPH developed in ~20–30% of patients, with 2–5% progressing to clinically overt disease requiring variceal banding, Transjugular Intrahepatic Portosystemic Shunt (TIPS), PSE, or management of liver failure. Latency to presentation was typically 4–10 years after oxaliplatin exposure. Common features included splenomegaly, thrombocytopenia, varices, and ascites. Histopathology consistently showed sinusoidal dilatation, congestion, perisinusoidal fibrosis, NRH, and microthrombi, confirming endothelial-mediated injury. Up to half of chronic cases were misclassified as metabolic dysfunction–associated steatotic liver disease (MASLD/NAFLD) or cryptogenic cirrhosis. Bevacizumab demonstrated consistent hepatoprotection, delaying splenic enlargement and reducing thrombocytopenia, likely via preservation of sinusoidal endothelial integrity and reduction of von Willebrand factor–mediated platelet microthrombi. Interventional radiology provided therapeutic options: in a prospective phase II study, PSE restored platelet counts >130×10⁹/L in 94% and enabled chemotherapy resumption within a median of 14 days, with no grade ≥3 adverse events. Conclusions: OIPH is an under-recognized complication of CRC chemotherapy, with latency spanning years after treatment. Splenomegaly and thrombocytopenia serve as early clinical signals, while misdiagnosis as MASLD or cirrhosis is common. Bevacizumab provides hepatoprotection, and PSE offers a safe and effective option for chemotherapy-limiting thrombocytopenia. Routine monitoring of spleen volume and platelet trends should be integrated into follow-up, and prospective validation of prophylactic and interventional strategies is urgently needed.

Abstract Introduction: CD20xCD3 bispecific antibodies (BsAb) have been approved for use in relapsed/refractory (RR) large B-Cell lymphomas (LBCLs) with manageable toxicities. The main adverse events of clinical interest are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The risk factors for CRS and ICANS are not well understood. Knowledge of variables that contribute to increased risk may help clinicians identify and tailor management for high-risk patients (pts) and increase the comfort level for providers using these therapies in community practices. Methods: We performed a multicenter retrospective study at 21 US centers evaluating pts with RR LBCLs receiving commercially available epcoritamab (epco) or glofitamab (glofit) between 2023 and 2025. We obtained baseline characteristics, safety and efficacy outcomes. Univariate analysis was performed to identify associations between CRS, ICANS, and clinical variables of interest. Results: As of May 31, 2025, a total of 312 pts with RR LBCLs were treated with BsAb, Epco n=193 (62%), Glofit n= 119 (38%); median age 68; 63% male; 70% ECOG PS 0-1. Most common histologic type was diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) (n=239, 84%) followed by high-grade B-cell lymphoma (HGBL) (n=46, 16%). 179 pts (57%) were previously treated with chimeric antigen receptor T-cell (CAR-T) therapy, with 47% receiving CAR-T &lt;6 months (mo) prior to BsAb. Among pts with prior CAR-T, CRS with CAR-T therapy of any grade occurred in 63%, with 26% ≥ grade 2. ICANS of any grade (G) occurred in 25% of pts (9.4% ≥ G3). Overall and complete response (ORR and CR) rates to BsAb were 51% and 29%, respectively. With a median follow up of 5 mo, median progression-free and overall survival (PFS and OS) were 2.3 and 7.3 mo, respectively. With BsAb treatment, CRS of any grade occurred in 117 (39%) patients: 24% G1, 8.7% G2, 4% G3, 1% G4 and 1% G5. The max grade CRS occurred most frequently after the third dose of epco (35%) and the first dose of glofit (23%). CRS was managed with additional steroids in 24% of pts and tocilizumab in 22%. 13% of pts experienced ICANS: 5.8% G1, 3.4% G2, 2% G3, 1% G4 and 0.3% G5. Factors that increased the risk for any grade CRS included: bulky disease ≥ 7.5 cm at time of BsAb treatment (OR 2.04, 95% CI 1.17 – 3.55, p = 0.012), elevated LDH (OR 2.56, 95% CI 1.45– 4.76, p = 0.002) and treatment with epco compared to glofit (OR 1.69, 95% CI 1.04- 2.77, p = 0.036). As G ≥2 CRS generally requires inpatient monitoring and management, we next compared the risk factors between pts with no CRS or G1 CRS and G ≥2 CRS. Factors associated with increased risk for high grade CRS included: bone marrow involvement by lymphoma (OR 3.47, 95% CI 0.97 – 11.3, p = 0.043), platelet count ≤ 75 (OR 2.46, 95% CI 1.21 – 4.87, p = 0.011), ≥ 2 extra nodal sites (OR 2.04, 95% CI 1.07 – 3.97, p = 0.032) and ≥G2 CRS with prior CAR-T (OR 3.35, 95% CI 1.13 – 9.97, p = 0.027). Factors that increased the risk for ICANS included: bulky disease (OR 2.67, 95% CI 1.28 – 5.49, p = 0.008), elevated Cr ≥ 1.5x ULN (OR 3.79, 95% CI 1.25 – 10.4, p = 0.012), elevated AST/ALT ≥ 3x ULN (OR 4.65, 95% CI 0.92 – 19.9, p = 0.042), low albumin (OR 2.85, 95% CI 1.49 - 5.5, p = 0.002), and co-occurrence of CRS with BsAb (OR 9.1, 95% CI 3.85- 25, p &lt; 0.001). No other clinical variables including older age, histologic subtype, ECOG PS, B symptoms, IPI score, cell of origin or histologic subtype, baseline labs such as ALC, CRP, fibrinogen or D-dimer were significantly associated with CRS or ICANS risk. There was no difference in ORR or CR rates in patients who experienced CRS or ICANS. Conclusions: Our analysis of pts treated with commercial BsAb for LBCL shows an increased risk for CRS and ICANs based on clinical variables that are routinely obtained at baseline including tumor bulk, sites of disease, laboratory parameters, and history of prior CRS with CAR-T therapy. Differences in baseline populations receiving epco and glofit treatments in this real-world analysis have been previously reported (Brooks et al, Blood 2025) and the comparative risk for CRS between these treatments remains unclear. Future plans including multivariable analysis may allow for development of a predictive model to identify pts at high risk of CRS and ICANS with BsAb treatment, potentially leading to prospective clinical trials evaluating prophylactic interventions for high-risk pts.

Abstract Introduction: Epcoritamab (epco) and glofitamab (glofit) are bispecific antibodies (BsAbs) approved for the treatment of patients (pts) with multiply relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Though response rates are relatively high, most patients (pts) eventually experience progression of disease (POD). We sought to investigate the treatment patterns and clinical outcomes following POD post-BsAb for r/r LBCL Pts, as this has not previously been described. Methods: We performed a multicenter retrospective study including 21 US centers evaluating pts with r/r LBCL receiving commercially available epco or glofit between 2023 and 2025. Baseline characteristics and outcomes were extracted from medical records. Efficacy and survival outcomes were assessed by site investigators and included overall response rate (ORR), complete and partial response (CR, PR) rates, progression-free survival (PFS) and overall survival (OS), analyzed using the Kaplan Meier method. Results: As of May 15, 2025, a total of 312 pts with r/r LBCLs were treated with BsAb, of whom a total of 168 (53.8%) pts experienced POD [104 of 193 (53.8%) treated with prior epco and 64 of 119 (53.8%) treated with prior glofit]. Pts with POD had a median age at BsAb start of 67 years (interquartile range [IQR] 58-76), most were male (68.4%), and the most common histology was diffuse large B-cell lymphoma not otherwise specified (n=122 [71.8%]). Sixty-seven of 168 pts (39.9%) with POD after BsAb had experienced primary refractory disease defined as failure to achieve PR or CR to frontline therapy. A total of 102 (60.7%) pts with POD to BsAb had received chimeric antigen receptor (CAR) T-cell therapy prior to BsAbs, with 33.3% of these pts being refractory to CAR T and 30.4% progressing within 6 months of CAR T-cell infusion. The median time to progression following BsAb start was 48 days. Following POD, 70 pts received no further anti-lymphoma therapy. Among 98 pts receiving subsequent therapy, 85 initially received systemic therapy and 13 initially received local therapy with radiation (concurrently with systemic therapy in 8 pts). The most commonly-used next line of systemic therapies included: loncastuximab tesirine in 19 pts (ORR 16.7%, all PR); commercial CAR T in 11 pts (ORR 50% [CR 36.4%, PR 18.2%); tafasitamab with lenalidomide in 7 (no responses); and other chemotherapy in 46 pts (ORR 27.6% [CR 24.1%]). The median follow-up time from POD was 9.2 months among survivors (95% confidence interval [CI] 7.8-13.3). Among those who initiated subsequent-line therapy following BsAbs, the median progression-free survival (PFS2) was 1.9 months (95% CI 1.5-2.4) and median overall survival (OS) from initiation of subsequent-line therapy was 3.9 months (95% CI 2.4-5.5). The estimated 1-year OS following initiation of next therapy was 12%. Conclusions: We report the outcomes of largest cohort of pts with POD post-BsAbs in r/r LBCL. Progression events occurred early after initiation of single agent BsAbs, and almost half of pts who progressed did not receive subsequent therapy. For those who received standard subsequent-line therapy after POD, response rates and survival outcomes were poor. Pts with POD after BsAB should be strongly considered for clinical trials of novel therapeutics or combination therapies.

Abstract Introduction: Epcoritamab (epco) and glofitamab (glofit) are bispecific antibodies (BsAbs) approved for the treatment of patients (pts) with relapsed or refractory (r/r) large B-cell lymphomas (LBCLs). Their use is associated with relatively high response rates, with some patients experiencing prolonged remission. It is unclear whether continuous treatment beyond 12 months for pts in remission is beneficial, as continued immunosuppression may result in additional toxicity. We sought to report the outcomes of pts with prolonged remission and survival following BsAb administration. Methods: We performed a multicenter retrospective study including 21 US centers evaluating pts with r/r LBCLs receiving commercially available epco or glofit between 2023 and 2025. Baseline characteristics and outcomes were extracted from medical records. Efficacy and survival outcomes were assessed by site investigators and included overall response rate (ORR), complete and partial response (CR, PR) rates. Pts who responded to BsAbs and had ≥365 days of follow-up from initiation of BsAb treatment were included in the analysis. Results: As of May 15, 2025, a total of 312 pts with r/r LBCLs were treated with BsAbs (epco n=193, glofit n=119) with a median age of 66 years (interquartile range [IQR] 59-73) at BsAb start. Most were male (64.5%), had advanced stage disease (77.4%) and had ECOG performance status of ≤1 (93.3%) at BsAb start. Of 207 pts who had initiated treatment with BsAb ≥12 months prior to data cutoff, we identified 31 pts (15.0%) who had a response to BsAbs (19 epco, 12 glofit) and were alive without progression at 12-months post-BsAb initiation and included them in this landmark analysis. Of the cohort of 19 pts treated with epco, 6 discontinued due to reasons other than disease progression including CAR-T cell therapy (n=2), secondary malignancy (n=2), allogeneic transplant (n=1), or other reasons (n=1). Thirteen of 19 pts received ≥12 months of epco treatment, and, with a median follow-up of 16 months from the start of BsAb, 12 of 13 pts continued receiving epco beyond 12 months with one pt discontinuing after 12 months (observed for an additional 41 days prior to censoring). Of the cohort of 12 pts treated with glofit, 8 pts were observed after completing all planned therapy and 4 patients underwent allogeneic transplant. Among all 31 BsAb-treated patients alive and in remission at 12 months, at the time of data cutoff, 5 pts (12.9%) had progressed (2 previously treated with epco and 3 with glofit). Three of the 4 pts who underwent allogeneic transplant after prior glofit treatment experienced disease relapse. A total of 24 pts (77.4%) were alive at the time of last follow-up, with the causes of death being disease progression (n=1), secondary malignancy (n=1), infection (n=1), and unknown cause (n=4). Conclusions: In this large cohort of r/r LBCL pts treated with BsAbs monotherapy in the standard of care setting, a relatively small proportion of pts (15%) achieve the 12 month PFS landmark. In the absence of robust evidence for what constitutes best practice, different strategies are employed, including continuation of BsAb, observation as well as consolidation with allogeneic transplant or CAR T-cell therapy. Additional follow-up will be reported to help guide clinical decision making regarding the optimal management strategy for this high risk pt population.