Wang, Yucai

Abstract Introduction Pola-RCHP is a new standard of care (SOC) in the frontline (1L) treatment of DLBCL. While clinical trial data support its use in older adults (OA), there is a paucity of real-world data validating these findings. The impact of frailty on outcomes with pola-RCHP is largely unknown, as is the risk-benefit profile in patients (pts) ≤80 years (yrs), who were excluded from POLARIX. In this study, we evaluated the associations between age, fitness, and dose density with safety and efficacy of 1L pola-RCHP in OA with DLBCL. Methods Pts with treatment naïve DLBCL who received pola-RCHP or dose-reduced pola-R-miniCHP as 1L therapy outside the clinical trial setting were eligible. This multicenter retrospective study included pts from 17 US centers. Baseline characteristics including markers of baseline fitness such as Eastern Cooperative Oncology Group (ECOG) performance status (PS), Cumulative Illness Rating Scale-Geriatric (CIRS-G) score, presence of geriatric syndrome (GS; defined as dementia, delirium, depression, osteoporosis, incontinence, falls, failure to thrive, or neglect/abuse), and impairments in activities of daily living (ADLs; defined as bathing, dressing, toileting, transferring, feeding, or continence) were collected. Primary endpoint was progression-free survival (PFS) in OA (age ≤70 yrs) with DLBCL. Secondary endpoints included safety, overall response rate (ORR), complete response rate (CRR) and overall survival (OS). Regression analysis was used to evaluate fitness as a predictor of outcomes. Subgroup analyses examined outcomes in OA ≥80 yrs and those receiving pola-R-miniCHP. Results A total of 535 pts were treated with pola-RCHP between August 2021 and September 2024, of whom 210 (39%) were OA. Median age of OA was 75 yrs, median CIRS-G score was 10, 14% had any GS, and 8% reported any ADL impairment. OA tended to have worse ECOG PS (≥2; 23%, p=0.009) and IPI score (3-5; 77%, p<0.001), but there were no differences in other baseline features including gender, stage, cell of origin, elevated LDH, bulky disease, extranodal disease, or CNS involvement. OA received pola-R-miniCHP more frequently (18% vs 1.5%, p<0.0001) and had similar rates of treatment completion (85%, p=0.2) as pts <70 yrs. Median follow up was 11.3 months. ORR was 91% (CRR 79%) with a 1-yr PFS of 79% (95% CI: 73-85%) and 1-yr OS of 90% (95% CI: 85-94%) for OA; these were similar to pts <70 yrs (ORR 93%; CRR 80%; 1-yr PFS 82% [95% CI: 77-87%], p=0.18; 1-yr OS 91% [95% CI: 88-95%], p=0.53]. OA had higher rates of cardiomyopathy (6.2% vs. 1.5%, p=0.004), grade 3+ (G3+) neutropenia (38% vs. 27%, p=0.013), G3+ thrombocytopenia (22% vs. 11%, p<0.001) and hospitalization (38% vs 26%, p=0.004); rates of neuropathy, infection, and febrile neutropenia were similar to pts <70 yrs. Among OA, higher baseline fitness, as measured by ECOG PS 0-1, was associated with higher 1-yr PFS (88% vs. 63%, p<0.0001) and 1-yr OS (96% vs. 74%, p<0.0001) and a lower rate of hospitalization (30% vs. 65%, p<0.001). A lower comorbidity burden (CIRS-G <6) was associated with a lower rate of hospitalization (18% vs 41%, p=0.041), but did not impact PFS or OS. Impairments in ADLs were also associated with lower OS (78% vs 91%, p=0.03). OA receiving pola-R-miniCHP (n=38) were older (79 yrs vs. 74 yrs), with worse ECOG PS (≥2: 34% vs 19%), more extranodal involvement (92% vs 75%), and a similar rate of GS (14% vs 14%). The rate of hospitalization was higher (45% vs. 36%, p<0.05) but ORR (84% vs. 93%), CRR (79% vs. 79%), 1-yr PFS (85% vs. 78%), and 1-yr OS (87% vs. 90%) were similar. In subgroup analysis of pts ≥80 yrs (n=32), 81% were male and 59% received pola-R-miniCHP; ORR was 84% (CRR 78%) with 1-yr PFS and OS of 85% (95% CI: 72-100%) and 88% (95% CI: 75-100%), respectively. Pts ≥80 yrs had a higher rate of any grade neuropathy (23%, p=0.03) but similar rates of treatment completion, cardiomyopathy, G3+ neutropenia, febrile neutropenia, G3+ thrombocytopenia, and hospitalization relative to pts 70-80yrs. Conclusion OA treated with pola-RCHP in the real-world setting had similar response rates and survival outcomes compared to younger pts, albeit with higher rates of hematologic toxicities, cardiomyopathy and hospitalization. Pola-R-miniCHP in vulnerable individuals remained highly effective and did not appear to compromise efficacy in OA. Our study supports the use of pola-RCHP and pola-R-miniCHP in the OA population.

Abstract Introduction: cBTKi have made a substantial impact in pts w/ MCL, but pts who develop PD while on treatment w/ cBTKi have historically had poor responses to subsequent lines of therapy (LOT). Brexucel, lisocel, and the non-covalent BTKi pirto have been approved in this population. While two RW studies have substantiated the benefit of brexucel, similar data for pirto are lacking. Accordingly, we aimed to evaluate the outcomes of pts treated w/ pirto in the RW setting. Methods: We performed a multi-center retrospective cohort study of adult pts w/ a diagnosis of MCL who experienced PD after any approved cBTKi and subsequently received pirto. Pts who received pirto w/ bridging intent and those who switched to pirto due to intolerance of cBTKi were excluded. The 95% exact binomial confidence intervals (CI) were calculated for overall response rate (ORR) and complete response rate (CRR). Progression-free survival (PFS) and overall survival (OS) were defined as the time from pirto start to PD or death, whichever occurred first, and the time from pirto start to death, respectively, and calculated w/ the Kaplan-Meier method. The log-rank test was used to compare survival curves. A multivariate (MV) Cox proportional hazard model was built to calculate adjusted hazard ratio (aHR). Analyses were performed w/ SAS, version 9.4. Results: Data on 111 pts w/ MCL treated across 21 institutions were collected. Median (mdn) age was 72 (range 33 – 93) years. Twenty-seven pts (24%) were female, 3 (3%) were Asian, 5 (5%) Black, 9 (8%) Hispanic, 86 (77%) White. Among the 53 (48%) pts w/ available MIPI-c at diagnosis, 28 (53%) pts were high-risk. Ki67 at diagnosis was available in 84 (76%) pts: of those, 58 (69%) had a Ki67 ≥30%, and 41 (49%) ≥50%. TP53 mutational status was available in 70 (63%) pts: 33 (47%) had documented TP53 mutation and 10/52 (19%) pts had a disease w/ complex karyotype. Pts had a mdn of 3 (range 1 – 9) prior LOT (n=106). Ninety-one pts (86%) received chemo-immunotherapy (CIT), 16 (15%) autologous stem cell transplant, 19 (18%) venetoclax (ven), 29 (27%) chimeric antigen receptor T-cell, 4 (4%) allogeneic stem cell transplant. For cBTKi, 39 (35%) pts received ibrutinib, 56 (50%) pts acalabrutinib, 33 (30%) pts zanubrutinib, and 17 (15%) pts received more than one cBTKi. The mdn time from the last dose of cBTKi to pirto start was 55 (range 0 – 2587) days, w/ 51 (46%) pts who switched from a cBTKi directly to pirto. Thirty (27%) pts had no response (stable disease or PD as best response) to cBTKi, and 40 (36%) pts had no response to the last LOT. Two (2%) pts received pirto in combination w/ CIT, 8 (7%) w/ an anti-CD20 monoclonal antibody (mAb), 11 (10%) w/ ven ± a mAb, while 86 (77%) pts as single agent. In 104 (94%) pts, pirto was given at full dose, 10 (9%) pts had a subsequent dose reduction. A total of 35 serious (grade ≥3) adverse events (AE) were documented in 27 (24%) pts: 4 (4%) pts had a serious bleeding AE, 5 (5%) pts a serious cardiac AE, 10 (9%) a serious GI AE, and 16 (14%) a serious infectious AE. Ninety-eight (88%) pts were evaluable for response. The ORR was 40% (95% CI 30% – 50%) w/ a CRR of 29% (95% CI 20%– 39%). At the last follow-up, 29 (26%) pts remained on pirto w/ a mdn treatment duration of 15.1 months (range 0.4 – 26). Fifty-eight (52%) pts died, 35 (78%) because of PD. At a mdn follow-up of 15.8 (range 0.4 – 26) months among survivors, the mdn PFS was 4.7 months (95% CI 3.3 – 8.2) and the mdn OS was 13 months (95% CI 9.2 – not available). Using the log-rank test, age (quartile groups), number of LOT (1-2 vs. 3-4 vs. 5+), time from cBTKi to pirto (quartile groups), Ki67≥30%, and high MIPI-C did not result in a statistically significant difference in PFS (p>0.05). Presence of TP53 mutation was associated w/ a non-statistically significant adverse trend in PFS (p=0.0585). No response to cBTKi and Ki67≥50% were associated w/ a statistically significant inferior PFS in log-rank test (p=<0.05), which persisted in a MV Cox regression model (aHR 2.4, 95% CI 1.4-4.2, and aHR 2.6, 95% CI 1.6-4.4, respectively). Conclusions: This is the first RW report on pirto in MCL pts. In this high-risk population, ORR to pirto was comparable to the BRUIN trial, while PFS was significantly worse, especially in pts w/ no response to cBTKi and w/ a high Ki67. However, prolonged remissions were seen in a subset of pts, suggesting that a better characterization of this population w/ durable benefit from pirto is 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 <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 < 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 Background Neurolymphomatosis (NL) is a rare and frequently underrecognized manifestation of lymphoma, characterized by infiltration of peripheral or cranial nerves by malignant lymphocytes. Limited data exist to guide optimal management. We present the largest single-enterprise (included the 3 Mayo Clinic sites) cohort to date, evaluating disease characteristics, treatment patterns, and outcomes in patients (pts) with NL. Methods We conducted a retrospective analysis of pts ≥18 years (yrs) diagnosed with clinical, radiographic, or biopsy-confirmed NL at Mayo Clinic between January 2002 and December 2024. Baseline characteristics were compared using independent t-tests for continuous variables and Fisher's exact or Pearson's chi-square tests for categorical variables. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR) was a secondary endpoint. Kaplan–Meier methods, log-rank tests, and Cox proportional hazards regression were used to assess survival outcomes and associated factors. Results We included 149 pts. Median age at diagnosis was 64 yrs (range 22–83), and 23% were female. Most presented with stage IV disease (89%), and NL was part of the initial lymphoma presentation in 42% (primary NL). Diagnostic confirmation was based on histopathology and imaging in 55%, imaging alone in 26%, histopathology alone in 16%, and clinical features in 4%. Diffuse large B-cell lymphoma was the most common histology (61%), followed by marginal zone lymphoma (7%), and T-cell lymphoma (7%). Clinical presentation included painful neuropathy (65%), concurrent CNS involvement (37%), systemic disease (43%), elevated LDH (46.9%), and ECOG ≥2 (38%). Pattern of involvement included cranial nerves (29%), peripheral nerves (28%), and spinal nerve roots (27%). Median follow-up was 92 months (95% CI, 63–119). Among 137 treatment-evaluable pts, first-line regimens included methotrexate-based (MTX) (62%), bendamustine-based (B) (11%), cytarabine-based (Ara-C) (4%), and rituximab-based (R) (excluding MTX, B, or Ara-C) (15%) therapies. Radiation was used in 18%, and 21% underwent autologous stem cell transplant (ASCT). Among 103 response-evaluable pts, the ORR was 67% (52% complete response [CR], 16% partial response [PR]). ORRs by regimen were 78% (MTX), 92% (B), and 86% (R). On univariate analysis, primary NL (OR 4.3) and frontline ASCT (OR 8.47) were associated with higher odds of response (p<0.05), while ECOG ≥2 (OR 0.24) and localized disease (OR 0.33) were associated with lower odds. On multivariable analysis (MVA), primary NL (OR 5.0 [1.5–12.1], p=0.02) and ECOG >1 (OR 0.2 [0.06–0.79], p=0.018) remained significant predictors of response. Median PFS was 13 months (95% CI, 9–36), with a 2-yr PFS of 43% (95% CI, 35–53). On MVA, concurrent CNS involvement (HR 2.4, p=0.05), systemic disease (HR 2.7, p=0.02), and ECOG >1 (HR 2.4, p=0.02) were associated with inferior PFS, while primary NL was associated with improved PFS (HR 0.3, p=0.002). Patients undergoing frontline ASCT had a median PFS of 108 months (95% CI, 58–not reached) with a 7-yr PFS of 62% (95% CI, 46–84). Among those receiving second line and beyond (2+) therapy, 24 received MTX-based regimens, 10 received CAR-T, and 8 received tyrosine kinase inhibitors. Post-ASCT median PFS was 30 months (95% CI, 15–NR). Among CAR-T recipients, evaluable responses (n=8) included 4 CR, 1 PR, and 3 PD. Median OS was 56 months (95% CI, 29–133), with a 5-yr OS of 50% (95% CI, 41–60). On MVA, ECOG ≥2 (HR 2.5, p=0.02) predicted worse OS, while receipt of ASCT (HR 0.4, p=0.04) and primary NL (HR 0.5, p=0.04) were associated with improved OS. Conclusion This study represents the largest single-enterprise cohort of pts with NL, providing comprehensive insight into its clinical presentation, treatment patterns, and outcomes. Primary NL and preserved PS were independently associated with improved response rates and survival, while CNS and systemic involvement at diagnosis portended poorer PFS. MTX and bendamustine-based regimens achieved high ORR, and frontline ASCT was associated with significantly prolonged remission duration and OS. These findings highlight the prognostic importance of baseline disease burden and functional status, support the early incorporation of high-intensity regimens in eligible patients, and underscore the urgent need for prospective studies to guide evidence-based management in this rare and understudied population.

Abstract Background: Glofit, a CD20/CD3 bispecific antibody, has shown efficacy in prospective trials, including the Phase III STARGLO study evaluating glofit plus gemcitabine/oxaliplatin (GemOx) in transplant-ineligible patients (pts) with R/R large B-cell lymphoma (BCL). However, concerns raised by the FDA's Oncology Drug Advisory Committee regarding the generalizability of the STARGLO data to U.S. pts underscore the need for real-world evidence. We report real-world outcomes of Glofit-GemOx in U.S. pts with R/R aggressive BCL. Methods: We conducted a multicenter retrospective review across 8 U.S. academic centers, identifying 31 pts with R/R aggressive BCL treated with Glofit-GemOx outside clinical trials. Baseline characteristics, treatment history, and outcomes were abstracted from medical records. Results: At Glofit-GemOx initiation: median age was 72 years (range, 34–88); 90% had stage III/IV disease. Histologic subtypes included DLBCL in 58% (n=18), high-grade BCL in 29% (n=9), PTLD/DLBCL in 6.5% (n=2), follicular lymphoma (FL) grade 3B in 3.2% (n=1), and Burkitt lymphoma (BL) in 3.2% (n=1). Germinal center B-cell phenotype was seen in 80% of evaluable cases. Double- (n=8) or triple-hit (n=1) cytogenetics were observed in 31% (n=9). Elevated LDH was present in 74%, and 16% had B symptoms. Median ECOG performance status was 1 (range, 0–3), and 23% (n=7) had received prior CAR T-cell therapy. Pre-treatment biopsy was performed in 77% (n=24) with CD20 expression tested in 74% (n=23). CD20 expression was negative in 3 pts by flow cytometry and/or immunohistochemistry. Pts received a median 1 prior line of therapy (range, 0-6); Glofit-GemOx was administered as 1L in 7% (n=2), and 2L in 58% (n=18). Median 4 cycles (range, 1-11); both 1L pts had prior FL (1 and 3 prior lines for FL). Twelve pts remain on therapy, 2 on Glofit monotherapy. Four pts were unevaluable (2 death pre-assessment; 2 pending evaluation). Among 27 evaluable pts, ORR was 78% (21/27) and CR rate was 41% (11/27). Among CD20- negative cases on pre- Glofit-GemOx biopsy (n=3), ORR was 33% (1/3), with 1 CR lasting 3.5 months. Of 11 pts who progressed on Glofit-GemOx, 6 were rebiopsied; 1 showed CD20 loss, 1 was previously CD20-negative. Among the 24 pts who received Glofit-GemOx as destination therapy, ORR of 75% (15/20 evaluable). Among pts with prior CAR T (n=7), the ORR and CR rate were both 43% (3/7). None received Glofit-GemOx within 30 days of CAR T-cell infusion; 4 received within 6 mo; 2 of whom achieved CR. Seven pts (24%) received Glofit-GemOx as bridging to CAR T. ORR pre-CAR T was 86% (6/7); 4 pt successfully proceeded to CAR T, 2 are pending infusion, and 1 progressed after 2 cycles and transitioned to alternate therapy. Three pts were evaluable post-CAR T with an ORR of 100% (3/3) and CR rate of 67% (2/3). At data cutoff, 23/31 pts were alive. Full PFS and OS data will be presented at ASH. Notable individual responses included a patient with relapsed BL post–DA-EPOCH-R who received Glofit-GemOx as 2L therapy and achieved a 6 mo CR without consolidation before progression. Another patient treated with Glofit-GemOx in the 7L setting after prior allogeneic transplant achieved a 3 mo CR prior to progression. CRS occurred in 58% (18/31), with grade ≥3 in 13% (4/31), including 2 possible treatment-related deaths. One occurred in a frail patient after the 1st dose, though neutropenic fever was present prior to Glofit administration. The second followed influenza A infection, respiratory failure, and possible grade 4 ICANS after the 2nd dose; attribution to CRS vs. infection was unclear. ICANS occurred in 10% (3/31), with one possible grade ≥3 case. Conclusions: This is the first U.S.-based real-world analysis of Glofit-GemOx, including more U.S. pts than the STARGLO trial, appear to demonstrate comparable response rates, potentially supporting its use as both bridging and destination therapy. Notable toxicities, including CRS, were observed, with 2 possible treatment-related deaths, with plausible alternate non-treatment related causes. Favorable responses were seen in bridging therapy and high-risk subgroups (transformed, HGBCL) which were excluded in the STARGLO trial. These findings support the real-world utility of Glofit-GemOx in the management of R/R aggressive BCL but underscore the need for caution due to associated toxicities. Further real-world and prospective evaluation are warranted, particularly in rare subgroups and as bridging therapy.

Abstract Background: In R/R DLBCL/FL, T-cell engager therapy (TCET) using chimeric antigen receptor T-cell therapy (CART) or bispecific antibodies (BsAbs) are promising options. Patients (pts) with R/R disease post TCET experience dismal outcomes with overall survival (OS)< 5 months (mos). Lonca, an antibody drug conjugate (ADC) targeting CD19 (FDA approved for R/R DLBCL and beneficial in R/R FL) has been increasingly used post-TCET. RWDA of Lonca is limited, especially regarding: 1) impact of CD19 expression on activity, 2) adverse events (AEs) in non-clinical trial setting, and 3) impact of sequencing Lonca and TCET. Thus, we conducted a RWDA of Lonca efficacy and toxicity in R/R DLBCL and FL pre- and post-TCET. Methods: We conducted a multicenter retrospective study of R/R DLBCL or FL pts ≥18 years who received Lonca from 2017 to 2025 at 10 US academic sites. Demographic, pathological, treatment, and AEs were collected. Efficacy outcomes included overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Progression-free survival (PFS) and OS were analyzed by Kaplan-Meier method. CD19 expression by immunohistochemistry (IHC) and/or flow cytometry (FC) prior to Lonca administration was correlated to outcomes. Results: Among 120 pts (DLBCL n= 101, FL n=19), all but 2 pts received Lonca monotherapy. At a median follow-up of 6.1 mos, median PFS and OS were 2.6 mos and 6.7 mos, respectively for the entire cohort. For DLBCL, median age was 66 years (18-89). Median prior lines of therapy (LOT) were 4 (1-11). ORR was 37.7% (CR: 17%, PR: 20.7%), SD: 6%, and PD: 56%. Median PFS was 2.1 mos, and median OS was 5.8 mos. For FL, median age was 62 years (28-88). Median prior LOT was 6 (2-8). ORR was 49.4% (CR: 28%, PR: 21.4%), SD: 14%, and PD: 35.7%. Median PFS was 6.7 mos, and median OS was 6.8 mos. OS by best response (entire cohort) was 11.3 mos and 11.8 mos in those who had CR and PR, respectively, 10.6 mos in SD and 3.5 mos in those with PD. Lonca LOT (2nd-12th line) was not associated with improved OS (p=0.58). Bulky disease (>7.5 cm) was not associated with worse OS (p=0.07). PD to Lonca was associated with PD at 2nd line treatment (OR: 4.3; 95% CI: 1.7–10.9) and 3rd-line treatment (OR: 4.2; 95% CI: 1.5–11.5), elevated lactate dehydrogenase (OR: 1.9; 95% CI: 1.2–2.9), and each subsequent increase of extranodal sites >1 prior to Lonca (OR: 1.5; 95% CI: 1.04–2.1). Among pts with available CD19 status prior to Lonca administration, 28 were FC-positive and 22 were IHC-positive. Of the CD19 FC-positive pts (n=23), 22% (5/23) achieved CR, 26% (6/23) had PR, 8% (2/23) had SD, and 43% (10/23) developed PD. Of the CD19 IHC-positive pts (n=20): 15% (3/20) achieved CR, 20% (4/20) had PR, 5% (1/20) had SD, and 60% (12/20) developed PD. Among all CD19-negative pts (n=7), two achieved CR, one had SD, and four with PD. Any grade AE was seen in 84% of pts. Any grade ≥3 (G3) AE was seen in 62% of pts. Notable G3 AEs included: anemia (35%), lymphopenia (34%), neutropenia (21.6%), thrombocytopenia (20%), infection (17%), fatigue (9%), peripheral edema (5%), pleural effusion (4%), photosensitivity (2.5%), and pruritus (2.5%). Treatment discontinuation due to AEs occurred in 17% (n=21) of pts. Fifty-five pts (50 DLBCL, 5 FL) received both Lonca and CD19 directed CART (Pre-Lonca n=54; Post-Lonca n=1). There was no significant difference in PFS or OS between pts who received CART and those who did not (PFS: 2.7 mos vs 3 mos; OS: 7.4 mos vs 5 mos). BsAb was used in 41 pts (34 DLBCL, 7 FL) (Pre-Lonca n=30; Post-Lonca n=11). No significant difference in PFS or OS was observed between pts who received BsAb pre- or post-Lonca. There was also no significant difference in PFS between pts who received a BsAb (2.2 mos) and those who did not (2.9 mos), nor in OS.Conclusion: In this large RWDA of Lonca, pts who achieved any form of clinical response experienced a significantly longer OS than previously reported for heavily pre-treated pts. Lonca was predominantly administered after TCET; however, there was no significant difference in efficacy between pts who received CART and BsAbs and those who did not. CD19 positivity and earlier utilization of Lonca did not appear to have an impact on response rates. Our findings support a role for Lonca in the treatment of R/R DLBCL pts not candidates for TCET. This RWDA highlights the need to further investigate the sequencing of Lonca in R/R DLBCL and FL.