Citations

Abstract Objectives Understanding whether the novel long-T ITC complex might assist in interpreting clinical prognostic utility compared to established cardiac biomarkers is needed. We determined long term major adverse cardiac events (MACE) and all-cause mortality (ACM) predicated on novel long-T ITC complex and high sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays in the emergency department (ED). Methods cTn assays were measured on the Mindray CL-1200i platform at presentation in consecutive patients enrolled in ‘Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon’ (MERITnI) (NCT05853042) trial with suspected ischemia. Sex specific 99th percentiles upper reference limits (URLs) were: hs-cTnI female 14 ng/L, male 15 ng/L; hs-cTnT female 10 ng/L, male 19 ng/L; long-T ITC complex 0.9 ng/L, same for female and male. Results Of 1,070 patients, 59.4 % were male, 43.4 % White, 45.5 % Black, and 39.5 % ≥65 years. Independent of biomarkers, a continuum of risk over 1 year showed MACE increased to 16.1 % and ACM to 16.5 %. Long-T ITC complex did not show a continuum change, increasing only 0.1 % (HR: 1.001 (1.0–1.001) per ng/L. However, hs-cTnI increased 1.8 % (HR: 1.018 [1.009–1.027] for each ng/L (p<0.0001) and hs-cTnT increased 0.3 % per ng/L (HR: 1.003 [1.001–1.006]) (p=0.0028). Between subjects ≤URLs and >URLs, MACE and ACM all biomarkers showed significant (p<0.0001) differences over 1 year. For MACE in those >URL long-T ITC complex increased 11.2–25.2 %, hs-cTnI 18.0–35.0 % and hs-cTnT 8.9–24.2 %. For ACM in those >URL long-T ITC complex increased 4.5–23.3 %, hs-cTnI 5.0–26.2 %, and hs-cTnT 3.6–24.1 %. Conclusions Novel long-T ITC complex did not provide new prognostic value to either hs-cTnI or hs-cTnT. Patients with increased hs-cTnI and hs-cTnT concentrations had marked increases in MACE and ACM risk at 1-year.

Abstract Background We determined whether circulating cardiac troponin I–cardiac troponin T–troponin C (ITC) complex containing long-form cardiac troponin T (long-T ITC) complex and ratios of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) could differentiate myocardial infarction (MI) from chronic and acute non-MI myocardial injuries in patients with suspected acute coronary syndrome. Methods We measured long-T ITC complex, hs-cTnI, and hs-cTnT (Mindray) at 0- and 2-h in consecutive patients enrolled in the Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon (MERITnI) trial. Results Among the 882 subjects studied (median 3.0 h presentation), 47 had acute MI (5.3%), 116 had acute non-MI myocardial injury, and 90 had chronic myocardial injury. At 0 and 2 h, areas under the curve (AUC) significantly differentiated acute MI from chronic myocardial injury for long-T ITC complex (0.72 and 0.81, respectively; P = 0.0082) but not acute non-MI myocardial injury (AUC, 0.65 and 0.69, respectively; P = 0.23). 0 and 2 h AUCs for long-T ITC complex/hs-cTnT and hs-cTnI/hs-cTnT ratios also significantly differentiated acute MI from chronic myocardial injury (AUC, 0.79 and 0.86, respectively) and acute non-MI myocardial injury (AUC, 0.68 and 0.71, respectively). There was no biomarker concentration or ratio value discrimination between type 1 and type 2 MIs. Conclusions Long-T ITC concentrations and long-T ITC complex/hs-cTnT and hs-cTnI/hs-cTnT ratios may clinically assist in differentiating acute MI from non-MI myocardial injuries when evaluating patients with suspected acute coronary syndrome. ClinicalTrials.gov Registration Number: NCT05853042.

ABSTRACT First‐line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. We conducted a phase 2 multicenter trial in the academic and community cancer research united (ACCRU) network, testing a multitargeted 1st line regimen. CARiBOU (ACCRU‐LY‐1804) employs alternating VR‐CAP and R‐cytarabine with continuous acalabrutinib, in six 21‐day cycles, for previously untreated MCL. The primary endpoint was complete metabolic response (CMR) rate. Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression‐free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was tested using the ClonoSEQ assay (Adaptive Biotechnologies). Of 41 patients enrolled, 39 (95%) responded to therapy, including 37 patients achieving CMR (90%). Two nonresponders discontinued therapy for toxicity early, prior to study‐defined restaging, and received alternate therapy. Undetectable MRD at a 10 6 threshold was achieved in 26/33 tested patients (79%), and 94% at 10 5 . 18‐month estimated PFS is 79% (95% CI 64%–97%), and OS is 96% (95% CI 88%–100%). Toxicities were primarily hematologic (grade 3 hematologic AE in 32 patients, [78%]). Twelve required platelet transfusions, and one grade 3 bleeding event occurred. Febrile neutropenia occurred in 4 patients, and 6 (14%) experienced SAEs. There were no treatment‐related deaths. CARiBOU is an efficient, highly effective outpatient 1st line MCL regimen, employing intermediate‐dose cytarabine and continuous acalabrutinib for 6 cycles. This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD‐guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791

Abstract Early pregnancy loss can have a profound impact on the lives of women and their families, but the experience is often underacknowledged, with the diverse and complex needs of these women not always being met. Health care providers are in a unique position to provide support, helping each woman navigate through what is often a significant event in her lifetime. In response to these gaps, a large academic medical center in the upper Midwest established the Early Pregnancy Care (EPC) Clinic in 2019 as a subclinic of the Department of Obstetrics and Gynecology. The goal of the EPC Clinic is to standardize the management of early pregnancy loss and related concerns to ensure each woman receives timely, holistic, and patient‐centered care that fully encompasses the physical and emotional needs of the patient and her family. The EPC Clinic is run by a small, dedicated team of certified nurse‐midwives and registered nurses in collaboration with a multidisciplinary team, providing comprehensive care to women with a confirmed early pregnancy loss, first trimester bleeding, pregnancy of unknown location, inconclusive viability, or a history of a prior early pregnancy loss, including ectopic and molar pregnancies. Team members coordinate timely visits and evaluation, offer comprehensive management options, and provide bereavement care and resources. Follow‐up care is arranged to monitor each woman's physical and emotional recovery following a loss, including check‐ins with consistent members of the team to maintain continuity of care. Anecdotal evidence as well as Press‐Ganey surveys obtained from patients and their families have demonstrated the exceptional value of the EPC Clinic. In this article, we outline our EPC Clinic's components and processes and discuss strategies that may benefit other health care systems aspiring to develop similar programs to improve early pregnancy loss care and the patient experience.

Abstract Introduction: First-line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. Multitargeted combinations, including optimized chemotherapy with novel agents targeted to MCL, may best address the biologic heterogeneity of this disease. Building on prior experience using modified VR-CAP and R-cytarabine, we enhanced this regimen by adding acalabrutinib while reducing cytarabine, aiming for improved efficacy and safety without impeding stem cell collection. To evaluate this regimen, we conducted a phase 2 multicenter trial at four centers in the Academic and Community Cancer Research United (ACCRU) network. Methods: CARiBOU (ACCRU-LY-1804) employs alternating VR-CAP and R-cytarabine with continuous acalabrutinib, in six 21-day cycles, for previously untreated MCL. Eligible patients (pts) were at least 18 years old with adequate organ function, measurable disease, no CNS involvement; and were ASCT-eligible per investigator. VR-CAP (cycles 1, 3, and 5) employed bortezomib 1.3 mg/m² subcutaneously days 1,8, and 15; rituximab 375 mg/m² day 1; cyclophosphamide 750 mg/m² day 1; doxorubicin 50 mg/m2 day 1; and prednisone 100 mg PO days 1-5. Cycles 2,4, and 6 used outpatient rituximab with cytarabine at 3 g/m² x 2 daily doses in the first 5 pts, after which the dose was reduced to 2 gm/m2 x 2 daily doses due to thrombocytopenia. Acalabrutinib 100 mg p.o. twice daily was given continuously but held for grade 4 thrombocytopenia or clinically significant toxicity. Growth factors and prophylactic antimicrobials were required. Responses were assessed after six cycles using FDG PET/CT, bone marrow aspirate/biopsy (BM Bx), and endoscopy when indicated (Lugano 2014). The primary endpoint was complete metabolic response (CMR) rate at end of treatment (EOT). Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression-free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was evaluated using the ClonoSEQ assay (Adaptive Biotechnologies). A Simon two-stage design was used, targeting a CMR rate ≥ 70% versus a null rate of 50%, with a total sample size of 39 evaluable pts. Results: 41 pts were accrued from October 2021 through May 2025, 37 of whom completed all 6 cycles and are evaluable for response; two are still on therapy, and two discontinued therapy early for toxicity. Median age was 63 years (range 41-73), 22% were female, and 85% were White. MIPI risk groups were low (44%), intermediate (39%), and high (17%), and Ki-67 was ≥ 30% in 54% of pts. Three pts (7%) had known TP53 mutations by sequencing. At EOT, the CMR rate was 85.3% among all pts (35/41; 95% CI 67.9%-92.9%), or 94.5% among evaluable pts (35/37). BM Bx was performed in 31 pts at EOT, 30 of which (96.8%) were negative for MCL. Undetectable peripheral blood MRD using a 10^6 threshold (uMRD6) was achieved at EOT in 78.1% (25/32) of tested pts, and 93.8% (30/32) achieved uMRD5. Nine of 41 pts underwent ASCT; no patient failed stem cell collection. Maintenance therapy was not protocol-defined but included rituximab in 91.9% of pts and a BTK inhibitor in 21.6% of pts. With a median follow-up of 16.7 months, PFS and OS rates at 18 months were 76.7% (95% CI: 60.7%-96.9%) and 95.5% (95% CI: 87.1%-100%). Toxicities were primarily hematologic. Grade 3+ toxicities included thrombocytopenia (66.6%), neutropenia (28.2%), and anemia (25.6%). Grade 3+ febrile neutropenia was observed in 10.2% of pts. Peripheral neuropathy was seen in 20.5% of pts and all grade 1-2. Bleeding events included purpura in 2 pts (5.2%) and epistaxis in 1 patient (2.6%). One case of atrial fibrillation was observed. Eighteen pts required temporary dose hold of acalabrutinib for toxicity (mainly thrombocytopenia), and 2 had acalabrutinib dose reductions. Serious adverse events occurred in 6 pts, and no treatment-related deaths occurred. Conclusions: CARiBOU is an efficient, highly effective outpatient regimen for 1st line MCL, employing intermediate dose cytarabine with continuous acalabrutinib. With supportive care and platelet monitoring, this approach safely yielded high rates of CMR and uMRD6, supporting multitargeted induction therapy for appropriate pts with untreated MCL.

Abstract Background Watchful waiting is a common option for pts with asymptomatic FL/MZL. Anti-tumor immunization may delay or even avoid subsequent need for more toxic therapies. EO is designed from non-self-protein sequences derived from gut bacteria, including 4 HLA-A2 CD8 T cell epitopes (synthetic mimic peptides), exhibiting molecular mimicry with specific epitopes on B cell markers (CD20, CD22, CD37, BAFF-receptor). EO also contains a CD4 helper epitope UCP2. EO expands pre-existing memory CD8 T cells recognizing non-self-epitopes from gut bacteria that cross-react with B cell antigens on tumor cells. Methods Cohort 2 (C2; planned accrual 25 pts) of EONHL1-20/SIDNEY includes HLA-A2+ pts with previously untreated FL/MZL not in need of treatment. Pts receive EO (300μg/peptide) SC with adjuvant Montanide, q2 weeks (w) x 4, then q4w, for 12 total doses. For antigen-specific immune responses, peripheral blood mononuclear cells were assayed by flow cytometry using EO-mimic or B cell peptide specific tetramers without in vitro stimulation. IFN-γ ELISPOT was used to evaluate response to UCP2 and anti-CD3. Primary endpoint is objective response rate (ORR) per Lugano 2014. A pre-defined futility boundary was applied (ORR uninteresting=5%/promising=20%). Finding at least 3 of 25 pts with ORR would meet criteria to continue development (chance of 13% and 90% for true ORR of 5% and 20%, respectively). Results As of July 2025, 22 pts had started EO. Median age 59 years (range 32-86); 9 female; 19 ECOG 0/3 ECOG 1; 19 FL/3 extranodal MZL (ENMZL); 3 Ann Arbor stage I-II/8 stage III/11 stage IV; FLIPI low risk 8/intermediate 8/high 6; FLIPI-2 low risk 12/intermediate 7/high 3; 19 GELF neg/3 pos. At a median follow-up for progression of 9.4 months, 9 pts completed EO, 4 stopped for progressive disease (PD), 2 due to PI/pt decision; 7 ongoing. Median treatment duration 38 w (range 4-39). Among 19 evaluable pts, best Lugano response was 3 complete (CR) and 6 partial responses (PR) (ORR 47% [95% CI 24%–71%]; CR-rate 16% [3%-40%]), 6 stable disease (SD), and 4 PD. ORR by PET-CT was 29% (n=14) w6, 39% (n=18) w19, 46% (n=13) w42; corresponding CR rates were 0%, 11%, 15%. Median time to response 17.1 w (range 5.3-41.1). Currently there are only 2 confirmed PD events in pts with prior PR/CR. Among 8 pts with an initial indeterminate response per LyRIC 2016 followed by a confirmatory scan, 4 pts did not have confirmed PD; a possible atypical response pattern rate of 50% on EO (occurring 5.3-41.9 w after start of EO). In 16 immune response evaluable pts, 88% and 81% had expansion of CD8 T cells specific for EO mimic and B cell target peptides, respectively. Expanded specific CD8 T cells had a memory phenotype dominated by effector memory (TEM) and central memory cells. At w5, 7 clinical responders and 7 non-responders were evaluable; more responders had a positive immune response against EO mimic (Chi-square p=0.025) and B cell target (p=0.047) peptides. Max expansion (response sum for 4 EO mimic or 4 B cell target peptides at a single timepoint w3-w8) of specific CD8 T cells (% of all peripheral CD8 T cells) was higher for responders than non-responders both for EO mimic (Mann Whitney p=0.018) and B cell target (p=0.017) peptides. Pts (4) with an initial indeterminate response (LyRIC 2016) had a higher max expansion of B cell target peptide specific CD8 T cells vs 4 pts with a typical progression pattern (Mann Whitney p=0.018) and vs all other 12 pts evaluable for immune response (p=0.029). There was no difference in CD4 T cell response to UCP2 in responders vs non-responders (induction or max immunity w3-w8). Anti-CD3 expansion of T cells indicating T cell intrinsic activation potential did not correlate with clinical response (baseline or max). The most common EO-related adverse events (AEs) were Gr (Grade) 1 (10 pts) and Gr 2 (6 pts) local administration site reactions. Other related AEs in &gt;1 pt were Gr 1 headache (3 pts) and Gr 1-2 fatigue (3 pts). Asthenia lasting 2 days was the only related Gr 3 AE. There were 4 unrelated Gr 3 AEs (gastroenteritis, GI-hemorrhage, inguinal hernia, and syncope). There were no Gr 4-5 AE. ConclusionsEO has a favorable safety profile and is preliminary associated with an ORR of 47%, exceeding the pre-specified boundary for promising activity. The speed and level of expansion of both EO mimic and B cell target peptide specific CD8 memory T cells are associated with objective response. Results will be updated.

Abstract Background Single-agent R is a common 1st-line therapy for patients (pts) with FL, especially those with low-tumor burden advanced stage disease or comorbidities. EO is a therapeutic vaccine generated from non-self-protein sequences from gut bacteria, including 4 HLA-A2 CD8 T cell epitopes that mimic B cell-specific markers: CD20, CD22, CD37 and BAFF-receptor. EO also contains a CD4 helper epitope UCP2. EO expands pre-existing memory CD8 T cells recognizing non-self-protein sequences from gut bacteria which can cross-react with B cell antigens on tumor cells. The aim adding EO to R is to safely increase the depth and duration of responses. Methods Cohort 3 (C3) of trial EONHL1-20/SIDNEY includes pts with HLA-A2 and previously untreated low-tumor burden (GELF) FL grade 1-3A in need of treatment (per pt/treating physician). Pts receive EO (300μg/peptide) SC with adjuvant Montanide, q2 weeks (w) x 4, then q4w for a total of 12 doses, combined with R starting at w7 (375 mg/m2 IV q1w x4, then q8w x4). For immune responses blood mononuclear cells were assayed by flow cytometry and EO-mimic or B cell peptide specific tetramers without in vitro stimulation. The primary objective is to assess safety; secondary objectives include EO immunogenicity and preliminary efficacy. Results As of July 2025, the 6 planned pts had started EO. Median age was 66 years (range 46-73); 5 ECOG 0/1 ECOG 1; 1 Ann Arbor stage III/5 stage IV; FLIPI low risk 2/intermediate 2/high 2; FLIPI-2 low risk 2/intermediate 4. At median follow-up 10.6 months (mo) 4 pts completed and 2 are ongoing on EO. Median treatment duration was 43 w (range 2-43). Best response by Lugano in the 6 pts included 4 complete (CR) and 2 partial responses (PR). Median time to PR/CR was 17.1 w (range 6.0-18.0). Currently there is only 1 (not yet confirmed) progression at 20.5 mo. All 5 immune response evaluable pts had expansion of CD8 T cells specific for EO mimic and B cell target peptides during treatment; 4 of 5 had detectable expansions at w5 (1st testing time). Currently, the longest tested immune response is at w65 and positive for both EO mimic and B cell target peptides. Expanded specific CD8 T cells had a memory phenotype predominantly composed of effector memory (TEM) cells but also including central memory (TCM) and terminally differentiated effector memory CD8 T (TEMRA) cells. Across the 5 pts, the medians of max % (sum of specific CD8 T cells targeting either the 4 EO mimic peptides or the 4 B cell antigen epitopes at a specific timepoint) among all peripheral CD8 T cells were 0.71% (range 0.19-3.97) for EO mimic and 0.33% (0.20-1.30) for B cell target peptides. The most common EO-related adverse events (AEs) were local administration site reactions (erythema, pain, induration). These included Gr (Grade) 1 reactions in 3 pts, Gr 2 in 1 pt, and Gr 3 in 1 pt; latter being ulceration with EO-interruption at w10.1, and in context of a strong immune response against EO mimic [3.97% of all peripheral CD8 T cells at w5] and B cell target [1.30%] peptides, and CR from w16.7. Other EO related AEs were Gr 1 lymph node pain (1 pt), and related to both EO and R were Gr 2 urticaria (1 pt) and Gr 1 fatigue (1 pt). Only R related were Gr 2 infusion related reaction (3 pts), Gr 2 enterocolitis infection (1 pt), and in 1 pt each Gr 1 flushing, anemia, headache and diarrhea. There were no further Gr 3-4 AE and no death on treatment/follow-up. Complete B cell depletion was seen in 5 pts tested at w18 (R added w7); no recovery in the range of w30-65. Only 3 infections were reported, per above enterocolitis, and 2 cases of COVID-19 both resolved without sequalae. ConclusionsThe combination of EO with R has a predictable and manageable safety profile, with EO only adding local administration site reactions to the well-known R safety profile. In this feasibility cohort all evaluable pts developed a specific immune response against EO and B cell targets, and a Lugano objective response. The combination of EO and R is feasible and can be evaluated in further trials. Updated results will be presented at the meeting.

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.