Introduction Liso-cel and axi-cel are CAR T cell therapies approved for 2L treatment of R/R LBCL. While both pivotal trials established superior efficacy versus standard of care, the absence of direct comparisons underscores the importance of RW comparative data to support informed treatment selection, toxicity management, and site-of-care planning. Objectives This study investigated the RW effectiveness, safety, and HCRU of liso-cel and axi-cel in the 2L treatment setting. Methods Patients with LBCL who received 2L liso-cel or axi-cel (April 2022–April 2025) were selected from the US Flatiron Health Research Database, an oncology-specific platform combining electronic health records and other RW data. RW OS and PFS were evaluated using Kaplan-Meier method. Descriptive statistics were used to describe safety endpoints (cytokine release syndrome [CRS], immune effector cell–associated neurotoxicity syndrome [ICANS], cytopenia) and HCRU (tocilizumab/steroid use, hospitalization). Further analyses adjusting for demographic and clinical covariates will be included in the presentation. Results The study included 473 patients with LBCL who received 2L CAR T cell therapy, with 198 receiving liso-cel versus 275 receiving axi-cel (median [IQR] age, 72 y [63–77] vs 63 y [54–70]; elevated LDH, 39% vs 33%; high-grade B-cell lymphoma, 41% vs 40%; receipt of bridging therapy, 78% vs 71%; bulky disease, 68% vs 74%; relapsed within 1 y of first-line treatment, 72% vs 86%; and median [IQR] follow-up time, 8 months [4–14] vs 12 months [5–22]).Early survival outcomes among patients in liso-cel versus axi-cel groups were similar at 6 months with no statistically significant differences observed (OS, 89% [95% CI, 84%–94%] vs 89% [85%–93%]; PFS, 69% [63%–77%] vs 71% [66%–77%]). CRS and ICANS of any grade were less frequent with liso-cel than axi-cel (CRS, 31% vs 64%; ICANS, 15% vs 34%), as were grade ≥ 3 CRS/ICANS (CRS, 1% vs 3%; ICANS, 3% vs 18%; Figure 1). Grade ≥3 cytopenia between day 30 to 89 after CAR T cell therapy infusion was less common with liso-cel than axi-cel (19% vs 28%). Patients in the liso-cel group were less likely to receive treatment for CRS/ICANS versus the axi-cel group (Table 1). Infusion in an outpatient setting was more common with liso-cel than axi-cel (21% vs 6%) and was associated with a lower rate of hospitalization after infusion (47% vs 62%; Table 2). For patients infused at an inpatient setting, liso-cel was associated with shorter length of stay (8 days vs 12 days) and lower rates of rehospitalization (33% vs 40%) compared with axi-cel. Conclusion In this retrospective RW analysis, liso-cel demonstrated similar effectiveness and a more favorable safety and HCRU profile versus axi-cel as a 2L therapy for R/R LBCL. Despite limited follow-up, these RW findings suggest liso-cel could deliver safety advantages without compromising efficacy in a broad population of patients with 2L LBCL.

ABSTRACT:Chimeric antigen receptor T-cell (CART) therapy has transformed the management of relapsed and refractory large B-cell lymphoma (LBCL), but real-world outcomes data is needed to confirm the benefits seen in clinical trial settings. We performed a multicenter retrospective analysis evaluating CART therapy outcomes according to line of therapy, specifically second line (2L) vs third line (3L) vs fourth line (4L) and beyond (4L+). We included patients who received CD19-directed CART therapy for de novo diffuse LBCL or transformed follicular lymphoma. Overall (N = 466), 21% (n = 98) of patients received CART as 2L, 41% (n = 192) as 3L, and 38% (n = 176) as 4L+. Median follow-up from CART infusion was 35 months. Overall response rate and complete response rate were similar for 2L vs 3L vs 4L+. From CART infusion, median progression-free survival (mPFS) and median overall survival (mOS) were similar for 2L vs 3L, but shorter in patients receiving CART as 4L+ (mPFS, 11.6 vs 12.7 vs 5.7 months, P< .001; mOS, not reached vs 69.4 vs 21.9 months, P< .001). In patients with double-hit or triple-hit lymphoma (DHL/THL), receiving CART in 2L vs 3L significantly improved 3-year OS (63% [2L] vs 32% [3L], P = .01). Patients with disease that required bridging therapy were also at increased risk of progression or death. Overall, our findings inform real-world practice wherein CART therapy as 2L vs 3L yields similar survival outcomes in unselected patients. However, patients specifically with DHL/THL should be considered for CART therapy in the 2L outside of the primary refractory disease (PRD) or early relapsed setting.

T-cell fitness can be impaired in patients with large B-cell lymphoma (LBCL) planned for CART (chimeric antigen receptor T-cell therapy). Although absolute lymphocyte count (ALC) at the time of leukapheresis has been shown to associate with outcomes in patients with LBCL treated axicabtagene ciloleucel (axi-cel), no threshold has been identified. This is a multicenter retrospective study including 1 axi-cel training and validation cohort, and 1 mixed-product validation cohort. The change-point method was used to identify an ALC threshold associating with optimal progression-free survival (PFS). Three hundred seventy-nine patients were included in the axi-cel training cohort. ALC as a continuous variable was associated with complete response on day 30 (median, 0.79 × 103/μL vs 0.63 × 103/μL; P = .004). An ALC of 0.34 × 103/μL was identified as the optimal threshold for PFS (7 vs 3 months; P = .0013). The association was confirmed in the axi-cel validation cohort (165 patients; 19.8 vs 3.5 months; P = .04) but not in the mixed validation cohort (163 patients; 5 vs 1.5 months; P = .3). On univariate analysis, characteristics associated with ALC above the threshold included low International Prognostic Index score (P = .02), low serum C-reactive protein level (P = .02), low serum ferritin level (P < .001), and low number of prior lines of systemic therapy (P = .02). An ALC of >0.34 × 103/μL at the time of apheresis is associated with optimal outcomes in patients with LBCL treated with axi-cel. A deeper investigation of the impact of prior therapies on the number and phenotype of lymphocytes at time of apheresis is warranted.

Mosunetuzumab (mosun) is a CD20xCD3 bispecific antibody approved for follicular lymphoma. Despite promising results in clinical trials, there are limited real-world data to assess outcomes with mosun, particularly in patients with poor performance status or significant comorbidities. To address this need, we performed a multicenter retrospective study at nine centers in the Collaborative US Bispecifics Consortium (CUBIC) and identified 119 patients who received mosun for non-Hodgkin lymphoma. Ninety patients (75.6%) had indolent lymphomas, 26% of whom would not have been eligible for the mosun registrational trial. Of these patients, 97% received single-agent mosun. Overall response rate (ORR) was 87% and complete response rate (CRR) was 71%. With median follow-up 17.0 months, median progression-free survival (PFS) and overall survival (OS) were not reached (NR). 18-month PFS and OS estimates were 56.7% and 92.9% respectively. Most cases of CRS or ICANS were low grade, with no differences in survival between trial-eligible and ineligible patients. There was a higher rate of infections in trial-ineligible patients than in trial eligible-patients (45% vs. 21%, p = 0.043). These findings support the use of mosun in the treatment of relapsed/refractory indolent lymphomas, even in trial-ineligible patients.

Abstract Bispecific antibodies (BsAb) approved for relapsed/refractory B-cell non-Hodgkin lymphomas (R/R NHL) redirect T-cells to malignant cells and have been associated with cardiovascular adverse events (CVAEs). We analyzed the FDA Adverse Event Reporting System (FAERS) data from December 2022 to September 2025 to characterize the safety of mosunetuzumab, glofitamab, and epcoritamab. Among 246,490 adverse event reports, 1,931 involved BsAbs. CVAEs occurred in 336 (17.4%) BsAb-associated reports of which 132 (39.3%) were fatal. The most frequent CVAEs were shock (3.2%), bleeding (3.0%), and hypotension (2.7%). As a class, BsAbs were associated with increased reporting of hypotension (aROR: 2.15, 95% CI = 1.48–3.13) and fatal CVAEs (aROR: 2.04, 95% CI = 1.60–2.60) compared to all other drugs in the FAERS database. Individual drugs showed distinct patterns: epcoritamab showed the strongest hypotension signal (aROR: 2.37, 95% CI = 1.55–3.62) and increased fatal CVAE reporting (aROR: 2.26, 95% CI = 1.72–2.98), while mosunetuzumab was associated with atrial fibrillation/flutter (aROR: 3.04, 95% CI = 1.53–6.03), supraventricular tachycardia (aROR: 2.72, 95% CI = 1.42–5.21), and tachyarrhythmias (aROR: 2.60, 95% CI = 1.44–4.72). CVAEs occurred earlier than non-CVAEs (median, 10 vs. 16 days, P < 0.001). Cytokine release syndrome occurred in 33.4% of BsAb-related adverse events, with hypotension most commonly overlapping (53.8%), while most arrhythmias occurred independently. These findings highlight cardiovascular toxicity signals associated with BsAbs and underscore the need for continued surveillance, risk stratification, and targeted cardiovascular assessment as these expand into broader clinical practice. However, consistent with the limitations of pharmacovigilance analyses, particularly the reliance on spontaneous adverse event reporting, these observations require confirmation in prospective studies.

Background Bispecific antibodies (BsAb) have improved outcomes for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Although these therapies show promising response rates, survival and durability of response remain limited and factors predicting survival outcomes remain unknown. Cumulative Illness Rating Scale-based comorbidity scores such as TRES and Severe4 have been shown to predict survival for B-cell NHL and for LBCL treated with CART, respectively. Here we report the impact of baseline comorbidities on outcomes of patients with LBCL treated with BsAbs. Methods We conducted a retrospective review of adult pts with LBCL treated with BsAbs outside of a clinical trial between June 1, 2023 and September 1, 2025 at 10 centers comprising the Collaborative US Bispecific Consortium (CUBIC). Response was assessed by institutional investigators. TRES and Severe4 were calculated as previously described (Gordon et al, 2023; Shouse et al, 2023). CRS and ICANS were graded by ASTCT criteria. Progression free survival (PFS) and overall survival (OS) were calculated from date of first BsAb dose and estimated using the Kaplan-Meier method. Results A total of 344 pts were included in the analysis (Table 1) with the majority having advanced stage disease (stage III/IV 87.9%, n=258). Patients received a median of 3 prior lines of therapy (range 1-11). Most pts had good performance status (ECOG 0-1 72%, n=226). The majority of pts received glofitamab (50%, n=172) and epcoritamab (45%, n=156). The overall response rate (ORR) for the group was 56% (n=174) with complete response (CR) rate of 38% (n=118). CRS occurred in 34% (n=118, G1:20.1%, n=69, G2:11.6%, n=40, G3:2.9%, n=10, G4:0.8%, n=3, G5:0.6%, n=2). After a median follow up of 9 months among survivors, 1 year PFS was 31% (95%CI:26-37) with median PFS 3.78 months (95%CI:3.48-4.9; Fig1A), while 1 year OS was 47% (95%CI:42-54) and median OS was 10.84 months (95%CI:8.51-14.19; Fig1B).Neither Severe4 nor TRES scores were predictive of PFS or OS (Table 2), while ECOG performance status was associated with inferior PFS (ECOG 0-1: median PFS 4.9 months [95%CI:3.75-6.37], ECOG≥2: median PFS 2.14 months [95%CI:1.58-3.65], p=0.00012, Fig1C) and OS (ECOG 0-1: median OS 14.23 months [95%CI:10.84-21.95], ECOG≥2: median OS 4.83 months [95%CI:2.76-8.34], p<0.0001, Fig1D). Conclusion In this large cohort of pts with LBCL treated with BsAb, baseline comorbidities assessed by Severe4 or TRES do not appear to predict survival, while ECOG≥2 was associated with inferior PFS and OS. Severe4 and TRES scores are based on severe comorbidities in the respiratory, upper GI, hepatic, renal, vascular and endocrine systems. These findings suggest that comorbidities may not preclude use of BsAbs in pts with LBCL. Evaluation of other comorbidities and clinical factors may yield additional prognostic markers in future studies.

PURPOSE:Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used. EXPERIMENTAL DESIGN:To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL. RESULTS:Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77-3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66-4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5-0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP. CONCLUSIONS:Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.

Mantle Cell Lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma, with frequent relapses and shorter responses with every subsequent treatment. MCL depends on growth factors and cytokines derived from microenvironmental cells for its growth and can alter the immune system to evade recognition and subsequent elimination. The soluble factors secreted by MCL can contribute to endothelial differentiation, lymphangiogenesis, and clonal selection under hypoxic conditions, thereby evading the DNA damage response. Targeting the tumor microenvironment and angiogenesis is an active area of research and development, as the angiogenic gene signatures in MCL remain poorly understood. To address this knowledge gap, we performed transcriptomic analyses of MCL patient cohorts and identified 10 key angiogenic genes upregulated in MCL. We focused on four receptors (FGFR1, VEGFR1, VEGFR2, and PDGFRB) that have receptor tyrosine kinase activity and are localized to the plasma membranes of MCL cells. These receptors were assessed for therapeutic targeting potential in four independent preclinical models, including patient-derived xenografts, cell-derived xenografts, bone marrow-derived xenografts, and a genetically engineered murine model of MCL. Our work establishes that simultaneous targeting of multiple kinases, such as FGFR1 and VEGFR2, is a promising therapeutic strategy for patients with MCL.

ABSTRACT:Chimeric antigen receptor T-cell therapy has revolutionized the treatment of relapsed/refractory (R/R) follicular lymphoma (FL). Real-world efficacy and toxicity data are needed because clinical trial populations are often unrepresentative. Therefore, we conducted a multicenter retrospective study of R/R FL patients undergoing commercial axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between 2021 and 2024. End points included efficacy measures (overall response rate [ORR], complete response rate [CRR], progression-free survival [PFS], and overall survival [OS]) and toxicity (rates of cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]). Among 136 patients, 100 (74%) received axi-cel and 36 (26%) received tisa-cel. Axi-cel patients were younger than tisa-cel patients (median age, 60 vs 68 years; P = .001) and received bendamustine lymphodepletion less often than them (9% vs 33%; P< .001). Median follow-up was 14.4 months (range, 0.8-72.0 months). In the unweighted analysis, compared with tisa-cel, axi-cel was associated with higher ORR (96% vs 80%; P = .007), CRR (88% vs 71%; P = .024), and longer median PFS (30.5 months vs 11.9 months; P = .021). Median OS did not differ significantly between the 2 products (not reached vs 23.6 months; P = .061). The rates of CRS were comparable (75% vs 75%; P = .99), whereas ICANS occurred more frequently with axi-cel than with tisa-cel (42% vs 17%; P = .008). After inverse probability of treatment weighting, efficacy outcomes were largely similar, but axi-cel remained associated with significantly higher toxicity. In real-world settings, both axi-cel and tisa-cel demonstrated efficacy in patients with R/R FL, although PFS was inferior to that reported in clinical trials.

Cardiovascular adverse events (CVAEs) associated with bispecific T-cell engaging antibodies (BsAbs) have not been systematically investigated across approved agents. In this disproportionality analysis of FAERS (December 2014-September 2025), reports listing BsAbs as the primary suspected drug (n = 7647) were compared with all other drugs in the database (N = 7 289 316) and appropriate active comparators. Adjusted reporting odds ratios (aRORs) were estimated using multivariable logistic regression, adjusting for age, sex, cardiovascular comorbidity, disease, and concomitant cardiotoxic medications. Among 7647 BsAb-associated reports (median age: 60 [36-71] years; 44.6% female), 1408 (18.4%) involved a CVAE and 447 (5.8%) were fatal. BsAbs showed increased reporting of DIC (aROR: 4.35 [3.18-5.96]; n = 49), hypotension (1.61 [1.38-1.89]; n = 181), and fatal CVAEs (1.63 [1.47-1.80]; n = 447). MM-directed BsAbs were associated with shock (2.09 [1.65-2.66]) and myocarditis (3.68 [1.49-9.10]). Blinatumomab was associated with DIC (4.41 [3.05-6.37]) and hypotension (1.46 [1.18-1.81]). Teclistamab showed the strongest myocarditis signal (5.95 [2.16-16.43]; n = 4). Mosunetuzumab showed increased reporting of atrial fibrillation (2.25 [1.15-4.38]) and supraventricular tachycardia (2.21 [1.17-4.15]). CVAEs occurred earlier than non-CVAEs (median 7 vs. 15 days; p < 0.001). The majority of hypotension (56.4%) and heart failure (44.2%) reports occurred independently of both CRS and infection. Case fatality proportions for shock (60.1%), DIC (51.0%), and heart failure (48.1%) exceeded those for CRS (24.3%). BsAb-associated cardiovascular signals, particularly DIC, hemodynamic events, and fatal CVAEs, varied by agent and target antigen. These findings support the need for cardiovascular-specific monitoring during therapy.

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare indolent B-cell lymphoma that is biologically distinct from classic Hodgkin lymphoma. Most patients present with limited-stage disease, and late relapses are common. The standard of care has evolved over the past decade with increasing use of rituximab-based chemotherapy regimens (Fanale, et al. Blood. 2017). NLPHL can transform into diffuse large B-cell lymphoma (DLBCL), however the incidence of histologic transformation (HT) and survival outcomes of transformed cases in the US population are unknown. The objective of this study was to describe the cumulative incidence and outcomes of transformed NLPHL in the US. We hypothesized that patients with transformed NLPHL would have significantly lower survival rates compared to de novo DLBCL. Method: We performed a population-based cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) program. We used the SEER-17 database, which captures cancer incidence and survival data representing 26.5% of the US population. We included patients aged 18-84 years old and diagnosed with NLPHL between 2010-2022. We identified patients with HT by following patients from diagnosis of NLPHL until their subsequent diagnosis of DLBCL. All patients had biopsy-confirmed HT. The study outcomes were relative survival (RS), overall survival (OS), lymphoma-specific survival (LSS), and the cumulative incidence of death from lymphoma (CIF). The lymphoma-specific CIF was used to account for the competing risk of death from other causes. The study covariates were age, sex, race, stage, B symptoms, prior receipt of chemotherapy, and prior receipt of radiation therapy. The study outcomes were modeled using flexible parametric survival models. Results: There were 1,700 patients with NLPHL included in the study. The median age at diagnosis was 46 years (interquartile range, 32-59), and most patients were male (n=1,118, 66%). After a median follow-up of 5.58 years, the cumulative incidence of HT was 2.59% (n=44/1700). The 5-year RS for patients without a history of HT was 97% (95% CI, 96-98%) compared to 88% (95% CI, 73-95%) for patients who subsequently transformed. Similarly, the other survival outcomes were also numerically worse for patients with HT (5-year OS, 93% vs 86%; 5-year LSS 97% vs 89%; and 5-year CIF 3% vs 11%). Next, we compared transformed NLPHL (n=44) with denovo DLBCL (n=61,784) diagnosed during the same time period. We found no significant difference in any of the study outcomes in the multivariable analysis. Using de novo DLBCL as the reference, the hazard ratios (95% CI) for transformed NLPHL were 0.53 (0.19-1.46) for RS, 0.55 (0.21-1.44) for OS, 0.57 (0.20-1.59) for LSS, and a subdistribution hazard ratio of 0.64 (0.26-1.58) for lymphoma-specific death. Conclusion: HT in NLPHL is an uncommon occurrence that is associated with a relatively good prognosis. In our study, patients who developed HT had similar 5-year survival rates compared to patients who never transformed. In addition, there was no significant difference in the outcomes of patients with transformed NLPHL and de novo DLBCL. Future studies will be needed to determine the impact of prior anthracycline-based chemotherapy on the outcomes of patients with transformed disease.

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell non-Hodgkin lymphoma (NHL) that predominantly affects patients with human immunodeficiency virus infection and is strongly associated with human herpes virus 8 (HHV-8) infection. Due to its rarity, the current understanding of PEL's epidemiology and management is largely derived from case reports and small retrospective studies. Using the SEER-17 database, we conducted a retrospective analysis of adults with pathologically confirmed primary effusion lymphoma diagnosed between 2001-2021. Patients were stratified into two time periods (2001-2010 and 2011-2021) to assess temporal trends. Age-adjusted incidence rates, relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) were calculated using flexible parametric survival models. Competing risk analysis was performed to evaluate cumulative incidence of lymphoma-specific death. Among 236 patients (median age 51 years, 88% male), 82 were diagnosed in 2001-2010 and 154 in 2011-2021. Age-adjusted incidence rates increased from 1.0 to 1.6 cases per 10,000,000 person-years between periods (p = 0.004). Five-year RS improved from 21% to 37%, with median OS increasing from 4 to 12 months. On multivariable analysis, the more recent period showed significant improvements in OS (HR = 0.65; 95% CI, 0.44-0.97) and LSS (HR = 0.56; 95% CI, 0.36-0.86), with reduced cumulative incidence of lymphoma-specific death (HR = 0.49; 95% CI, 0.33-0.74). In our population-level analysis of PEL, we report a significant improvement in survival outcomes between 2001-2021, likely reflecting advances in both lymphoma treatment and HIV management. However, despite these improvements, OS remains low underscoring the need for prioritizing these patients to clinical trials with novel therapies.

Cardiovascular toxicity is an increasingly important limitation of effective contemporary cancer therapies. Yet, the extent to which trials focus on preventing cardiotoxic events in patients receiving contemporary therapies is unknown. Leveraging PubMed, CENTRAL, clinicaltrials.gov, and publicly available reviews to identify all randomized controlled trials (RCTs) testing interventions for prevention or management of cardiotoxicity in cancer patients through 2024, we assessed the proportion of cardiotoxicity prevention trials that studied contemporary cancer therapies (biologic, targeted, or immune-based therapies). We included RCTs of interventional therapies/strategies against cardiotoxicity during cancer treatment. Data on trial baseline characteristics, design, funding, and reporting were extracted. Regression models were used to define trial and population factors associated with drug selection, reporting bias, and subsequent translation into guidelines. Overall, there were 126 trials, evaluating 15 prevention strategies, enrolling 16,111 participants (45.6 ± 13.9 years, 81.3

ABSTRACT Background Tafasitamab, a CD19‐targeting immunotherapy, is approved in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B‐cell lymphoma (R/R DLBCL) ineligible for autologous stem cell transplant. This real‐world study describes patient characteristics, treatment patterns, and outcomes associated with tafasitamab for R/R DLBCL across US practice settings. Methods A retrospective physician‐abstracted chart review was conducted among US adults initiating tafasitamab (with/without lenalidomide) for R/R DLBCL as part of routine clinical care. Data were summarized using descriptive statistics. Cox proportional hazards‐based analyses were performed to determine baseline characteristics associated with real‐world progression‐free survival and overall survival. Results Twenty‐three physicians (83% community physicians) provided data on 181 patients (64% White; median follow‐up since initiation, 14.7 months) meeting eligibility criteria. Most patients (72%) received tafasitamab as second‐line (2L) therapy. Real‐world overall response rate (95% CI) to tafasitamab was 73.5% (67.0–79.9). Median (95% CI) real‐world progression‐free survival and overall survival from tafasitamab initiation were 11.3 (9.8–13.6) and 24.8 (17.8–NE) months, respectively. In multivariable Cox proportional hazards‐based analyses, tafasitamab use in third‐line to fifth‐line (3L–5L) (vs. 2L), bulky disease (vs. non‐bulky), Ann Arbor Stage III–IV (vs. stage I–II), and increasing Charlson Comorbidity Index scores were determined as factors associated with increased progression risk. In addition, increasing age, tafasitamab in 3L–5L (vs. 2L), bulky disease (vs. non‐bulky), and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2 (vs. < 2) were associated with higher mortality risk. Conclusion This analysis of a diverse US population who received tafasitamab for R/R DLBCL predominantly in community practice settings supports the clinical benefit of tafasitamab. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Abstract Epcoritamab is a US Food and Drug Administration–approved bispecific antibody for relapsed/refractory (R/R) large B-cell lymphomas (BCLs). Real-world outcomes and safety data remain limited. We analyzed 157 adult patients with R/R aggressive BCLs who received epcoritamab outside of a clinical trial between 2023 and 2025 at 9 centers in the Collaborative US Bispecific Consortium. The best overall response rate (ORR) was 49.6%, and the best complete response rate (CRR) was 31.9%. With a median follow-up of 15.8 months, the 1-year progression-free survival (PFS) and overall survival (OS) rates among all patients were 29% (95% confidence interval [CI], 22-37) and 38% (95% CI, 31-47), respectively. Inferior ORRs and CRRs were observed in patients with high International Prognostic Index, elevated lactate dehydrogenase (LDH), ≥2 extranodal sites, and disease refractory to the previous line of therapy (LOT). In multivariable analysis, Eastern Cooperative Oncology Group performance status score of ≥2, elevated LDH, refractory disease to previous LOT, and clinical trial ineligibility were associated with inferior PFS and OS. Among all patients, 33% had any-grade cytokine release syndrome (CRS; grade ≥3, 4.6%), whereas immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 12% (grade ≥3, 0.6%) of patients. Intensive care unit (ICU) admission occurred in 17% of patients. Compared with pivotal trials and other real-world studies, we observed inferior response rates and survival outcomes as well as higher rates of grade ≥3 CRS, any-grade ICANS, and ICU admission.