Pophali, Priyanka A.

Abstract Background Several bispecific antibodies (BsAbs), including mosunetuzumab, glofitamab, and epcoritamab, are approved for non-Hodgkin lymphoma (NHL). However, real-world patient-centered data evaluating treatment-related time burden and preferences are lacking. Methods We conducted an online survey of 120 patients with relapsed/refractory follicular lymphoma (FL; N = 60) and diffuse large B-cell lymphoma (DLBCL; N = 60) receiving BsAbs. Participants reported all-cause healthcare visits and time spent on cancer-related healthcare resource utilization over the past 30 days, including travel, treatment administration, recovery, and impact on daily activities. Participants also evaluated two hypothetical treatment profiles to assess preference for fixed-duration versus treat-to-progression therapy. Results Participants with FL reported a mean of 2.5 healthcare visits in the past 30 days, with significantly fewer visits for mosunetuzumab versus epcoritamab (1.7 vs 3.3, respectively; P < .01). In DLBCL, the mean was 2.6 visits, with fewer visits for glofitamab versus epcoritamab (2.2 vs 3.0; P =.01). Although epcoritamab visits were shorter in FL, more frequent visits and longer recovery time resulted in significantly lower monthly time burden with mosunetuzumab versus epcoritamab (31.2 vs 61.9 hours; P < .05). Similarly, monthly time burden was also lower with glofitamab than epcoritamab in DLBCL (43.0 vs 87.7 hours; P < .05). Most participants reported little to moderate impact on daily activities. Across treatment groups, ≥92% preferred a hypothetical fixed-duration regimen over a treat-to-progression therapy. Conclusion Our real-world data, including novel aspects of time toxicity, demonstrate clinically meaningful differences in time burden associated with BsAbs and emphasize the importance of incorporating patient convenience and preference into shared decision-making in NHL.

Abstract The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient and disease characteristics. In the landmark analysis, rituximab maintenance was associated with improved event-free survival (EFS; median, 49.9 vs 29.7 months; P< .001) as well as overall survival (OS; median, 109.5 vs 74.2 months; P< .001). The EFS and OS benefits were observed across most of the subgroups. EFS and OS differences were statistically significant in those who achieved a complete response to 1L BR (n = 590; median EFS, 62.7 vs 31.1 months [P< .001]; median OS, 136.1 vs 75.3 months [P< .001]), but the analysis among those who achieved a partial response to 1L BR was limited by the small sample size. These results provide additional evidence for the survival benefit of rituximab maintenance after BR in MCL and support its use in clinical trial design and routine practice.

Abstract Introduction: Older adults (OAs) with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients (pts). NAVD has been widely adopted in clinical practice for frontline (1L) treatment of OAs with advanced stage cHL based on the subset analysis of S1826 study (Rutherford et al, JCO 2025) showing a 1-year progression-free survival (PFS) of 93% and 1-year overall survival (OS) of 95% after NAVD (n = 50) which remained durable on longer-term follow up. Another phase 2 study (Torka et al, JCO 2025) showed that NAVD is a highly effective and well-tolerated 1L regimen in OAs with cHL (n=40) across a wide range of geriatric impairments. Adverse events (AEs) and efficacy have not been reported in OAs treated with NAVD outside of a clinical trial. Hence, we sought to evaluate safety profile and efficacy outcomes of OAs with cHL treated with 1L NAVD in a real-world setting (RWS). Methods This is a multicenter retrospective cohort study of adults (≥18 years) with cHL treated with 1L NAVD between 2023 and 2025 at 20 US academic sites. Baseline characteristics and outcomes of pts ≥60 years were evaluated as a pre-planned subset analysis. The safety evaluable cohort received at least 1 cycle of NAVD and included pts who had not yet completed treatment. The efficacy evaluable cohort had completed 6 cycles of treatment including end of treatment (EOT) PET-CT and included pts who intended to complete treatment but died or discontinued due to progressive disease or AEs. The primary endpoint was EOT overall response rate (ORR). Secondary endpoints included EOT complete response rate (CRR), PFS and OS. PFS and OS were analyzed using the Kaplan Meier method. Results Among 311 pts, 81 were OAs (26%). Median age of the OA cohort was 70 (range 60-88) yrs, 65% male, 84% Caucasian, 71% nodular sclerosis subtype, 58% stage 4 disease, 59% B symptoms, 14% bulky disease (>7.5 cm), 69% extranodal sites, 41% EBV positive, 54% hypoalbuminemia, 49% IPS ≥ 4 and10% had an autoimmune disease. G-CSF was given in 81% pts. All 81 pts were evaluable for safety; 74% experienced a grade 3+ (≥G3) AE, 54% had ≥G3 hematological AE, 48% had ≥G3 neutropenia, 17% had febrile neutropenia. Infection rate was 28% with 10% ≥G3, neuropathy rate was 23% with 4% ≥G3. One infusion reaction was noted. Treatment related hospitalizations rate was 23% with median duration of 7 (range 1-16) days. There were 24 immune related AEs (IrAE) (30%) of which 5 were ≥G3. Most common IrAE was hypothyroidism (n=5), followed by inflammatory arthritis (n=4), pneumonitis (n=2, ≥G3, n=1), hepatitis (n=2, both ≥G3), adrenal insufficiency (n=2, ≥G3, n=1), colitis (n=2), and rash (n=2). One patient each had autoimmune neutropenia, sarcoidosis of lung/skin and myocarditis (≥G3). Overall, 15% pts required steroids with resolution of IrAEs in 56% cases, 30% (n=7) pts required continued therapy (levothyroxine in 4 pts, steroids in 3 pts, medical tx for heart failure in 1 pt). Treatment was interrupted in 22%, reduced in 22%, and discontinued in 23% pts. Nivolumab was discontinued in 14% pts. Among all pts (n=81), 81% had an interim PET-CT after 2-4 cycles. The ORR and CR rate at interim PET-CT were 100% and 81%, respectively. In the efficacy evaluable pts (n=52; 24 still on therapy), the EOT ORR and CRR were 93.2% and 84% in OAs compared to 96.8% and 91.7% in pts <60yrs, respectively. At a median follow up of 10.2 mo (range 0.27-28.52), the 1-yr PFS was 90.6% (95% CI: 82.7%-99.3%) in OAs and 95.5% (95% CI: 91.6%- 99.6%) in pts <60 yrs (p=0.044). 1-yr OS was 97.5% (95% CI: 94.1-100%) and not evaluable in pts <60yrs (p=0.017). None of the baseline features were predictive of response, additional analysis to understand impact on AEs and survival is ongoing. Among the 5 pts with progression/relapse, 4 were primary refractory. 4 pts received 2nd line (2L) therapy.79 pts are alive at data cut off, 2 deaths occurred- 1 infection-related and other unknown; both after the 1st cycle. Conclusions In this largest RWS cohort of OAs treated with NAVD we showed comparable response rates, AEs and 1-year survival outcomes to those in the pivotal S1826 trial. Notably, rates of ≥G3 AEs including infections, neuropathy and IrAEs remained low and manageable. Although survival significantly improved with NAVD compared to historical data, outcomes of OAs remained inferior compared to pts <60 yrs. Our data reinforces the use of NAVD as the preferred 1L option for OAs with advanced stage cHL.

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 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: Anti-CD19 chimeric antigen receptor T-cell (CART) therapy is feasible with an acceptable safety profile in older patients (pts) with relapsed/refractory (RR) large B-cell lymphoma (LBCL) (Tun et al, AJH 2024). However, immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and challenging toxicity in older pts, and its characteristics and associated risk factors are not well defined. Methods: Seven centers participated in this retrospective study. Pts aged ≥65 years (yrs) with RR LBCL treated with a commercial CART product were included. Baseline characteristics, treatment, CART toxicity, and outcomes were collected. ICANS was graded by the ASTCT criteria in most pts. Cumulative incidences of ICANS were estimated using deaths/progressions as competing risks, and associations between incidences and variables were assessed by Gray's test. A 30-day landmark was set after infusion to reduce immortal time bias. Progression-free survival (PFS; time from the landmark to disease progression or death) and overall survival (OS; time from the landmark to death) were analyzed with the Kaplan-Meier method. Statistical analyses were done in JMP v18. Results: A total of 224 pts were included. Median age at infusion was 71 yrs (range 65–89; ≥80 yrs, 12%. 142 (63%) were male and 27 (13%) had an ECOG PS scale of ≥2. The median HCT CI was 1 (range 0–6). LDH was elevated in 110 (51%) pts, 23 (19%) had bulky disease ≥7 cm, 176 (82%) had advanced-stage, and 145 (71%) had extranodal disease. Median number of prior treatments was 2 (range 1–8), and 44 (20%) had prior bendamustine. Prior stem cell therapy was done in 47 (21%) pts (autologous stem cell transplant [SCT], n = 45; allogeneic SCT, n=2). Axicabtagene ciloleucel (axi-cel) was most frequently used (58%; n=131) followed by lisocabtagene maraleucel (liso-cel) (16%, n=36) and tisagenlecleucel (tisa-cel) (25%, n=57). Median duration of ICANS was 6 days (interquartile range [IQR] 3–11; range 1–303). Median time to ICANS onset was 6 days (IQR 3.8–8.0; range 0–24). The 30-day cumulative incidence of all grade ICANS was 50.9% (95% confidence interval [CI] 44.7–57.9) and grade ≥3 ICANS was 29.8% (95% CI 24.0–37.0). There was no significant difference in incidence of all grade (P=0.39) and grade ≥3 (P=0.49) ICANS as well as duration of ICANS (≥14 vs <14 days; P=0.08) according to the age groups (≥65–69 vs ≥70–74 vs ≥75–79 vs ≥80–89). In contrast, pts with an ECOG PS scale of ≥2 were associated with a higher incidence of all grade (30-day estimate, 66.7% vs 47.0%; P=0.02) and grade ≥3 ICANS (30-day estimate, 53.8% vs 25.6%; P=0.002). In addition, pts with an elevated LDH level had a higher incidence of grade ≥3 ICANS than those without (30-day estimate, 37.5% vs 18.8%;P=0.004). The incidence of ICANS varied among various CART products, with 30-day estimates of 64.9% vs 33.3% vs 29.8% (P<0.0001) for all grades and 40.1% vs 13.2% vs 18.0% (P=0.004) for grade ≥3 ICANS in pts treated with axi-cel vs tisa-cel vs liso-cel, respectively. A trend toward higher grade ≥3 ICANS was seen in pts treated with ≥3 prior lines than those treated with 2 or 1 (30-day estimate, 35.7% vs 28.1% vs 10.5%; P = 0.07). ICANS was managed with steroids in 47 (41%) pts, levetiracetam +/- other agents in 46 (40%) pts, biologic agents +/- other drugs in 15 (13%) pts, and supportive care in 6 (5%) pts. Median follow-up from the 30-day landmark post-infusion was 17.2 months (95% CI 14.2–22.4). Median PFS was 10.5 months (95% CI 5.7–18.2) and OS was 18.2 months (95% CI 13.3 vs 27.5). There was no difference in PFS and OS in pts who experienced ICANS vs no ICANS (median PFS 14.7 vs 10.1 months; P=0.65 and median OS 18.2 vs 24.7 months; P=0.49). However, there was a trend toward inferior PFS and OS in pts who experienced high-grade ICANS compared to those who had grade 0-2 ICANS (median PFS 9.2 vs 21.2; P=0.14 and median OS 11.7 =vs 22.9; P=0.39). Conclusions: This large study of older pts with RR LBCL demonstrated acceptable risks of ICANS, comparable to that in pivotal registration trials, with a relatively higher rate of grade ≥3 ICANS. The risks of ICANS were similar regardless of patient age, including those aged ≥80 yrs, but different among CART products. Similar to younger pts, high tumor burden disease and poor performance status at CART infusion were associated with higher risks of ICANS. A comprehensive neurologic and frailty assessment is warranted to identify suitable CART candidates.

Abstract Introduction: NAVD has become a standard-of-care for frontline (1L) treatment (tx) of advanced stage cHL, based on the results of the S1826 study. S1826 demonstrated a 1-year progression free survival (PFS) of 94% for NAVD compared to 86% for brentuximab vedotin-AVD, which remained durable at 2 years (Herrera et al, NEJM 2024). Adverse events (AEs) and efficacy have not been reported in patients (pts) treated with NAVD outside of a clinical trial. Hence, we sought to evaluate safety profile and efficacy outcomes of pts with cHL treated with 1L NAVD in a real-world setting (RWS). Methods: In this multicenter retrospective cohort study, we included pts ≥18 years with cHL treated with 1L standard of care NAVD between 2023 and 2025 at 20 US academic sites. The safety evaluable cohort received at least 1 cycle of NAVD and included pts who have not completed tx. The efficacy evaluable cohort had completed 6 cycles of tx including end of treatment (EOT) PET-CT and included pts who intended to complete tx but died or discontinued due to progressive disease or AEs. The primary endpoint was EOT overall response rate (ORR). Secondary endpoints included EOT complete response rate (CRR), PFS and overall survival (OS). PFS and OS were calculated from the start date of tx and analyzed using the Kaplan Meier method. Results: A total of 311 pts with cHL were treated with NAVD with 26% of pts with tx ongoing (n=83) and 73% with tx completed (n=228). Baseline demographics included 55% male pts, 60% with stage IV disease (stage IIB, n=4) and 84% with nodular sclerosis subtype. Median age was 37 years (range 18-88), 29% had bulky disease (>7.5 cm), 28% were EBV positive (n=74/268), 8% had history of an autoimmune disease, and 31% had an IPS 4-7. G-CSF was given in 64% of pts. All patients were safety evaluable. Tx was interrupted (any length) in 24%, reduced in 12%, and discontinued in 14%. The most common reason for dose reduction was neuropathy in 4%. Nivolumab was discontinued in 10% and all therapy in 3.7% due to toxicity. Any AE and any grade 3 or higher AE (>G3) were observed in 92% and 62%, respectively. Neutropenia of any grade occurred in 68% (48% >G3), infection in 25% (10% >G3), and neuropathy in 30% (2.8% >G3). Hospitalization for an AE occurred in 20% (4.5% febrile neutropenia). Among pts with complete data (n=305), any immune related AE (irAE) occurred in 78 pts (25.6%) with any >G3 irAE in 23 pts (7.5%). The most common irAEs included hypothyroidism (7.9%, all grade 1-2), hepatotoxicity (1.6% G1/G2, 3.3% >G3), inflammatory arthritis (3% G1/G2, 0.6% >G3), rash (2.6%, all grade 1-2), and colitis (1% G1/G2, 1% >G3). Other notable >G3 irAEs included adrenal insufficiency (n=2), AKI/ATN (n=1), myocarditis (n=1), diabetes (n=1) and pancreatitis (n=1). Of 84 irAE events, 47 (56%) have had complete resolution. Among all pts, 14.4% (n=45) required systemic steroids at any time (intravenous in 4.1%), 3.2% (n=10) require ongoing steroids/immunosuppression and 8.3% other therapy for an irAE (n=23 levothyroxine, n=1 hemodialysis, n=1 heart failure tx, n=1 insulin). Among all pts, 265 (85%) had an interim PET-CT after 2-4 cycles. The ORR and CRR at interim PET-CT were 97% and 78%, respectively. In the efficacy evaluable population (n=228), the EOT ORR and CRR were 96% and 90%. The median follow up was 10.2 mo (range 0.27-28.52). The 1-year PFS and OS estimates were 93.8% (95% CI: 90.8-98.4%) and 99.1% (95% CI: 97.9-100%), respectively. In multivariable analysis (MVA), only IPS score (OR 0.6, 95%CI: 0.59-0.60) was associated with lower CRR. In Cox univariable analysis, EBV+ status (HR=14.8, 95% CI: 3.2-69.2), IPS score (HR=1.5, 95% CI: 1.0-2.2), and ESR (HR=1.02, 95% CI: 1.00-1.04) were associated with worse PFS. Among the 11 pts with progression/relapse, 9 were primary refractory. 10 pts were started on second line (2L) therapy, and all pts are alive (1 pt pending 2L tx initiation). There were 2 deaths: one related to infectious complications and other unknown and both occurred after the first cycle of therapy. Conclusions: Pts treated with NAVD in a large RWS showed comparable response rates and 1-year survival outcomes to those in the pivotal S1826 trial. Most AEs were similar and grade 1-2, but close monitoring of irAEs is necessary given the potential long-term toxicity of checkpoint inhibitors and potential for ≥G3 irAEs (7.5%) in this young patient population. Our data supports the use of NAVD for 1L advanced stage cHL.

Abstract Background Chimeric antigen receptor T-cell (CAR-T) and bispecific antibody (BsAb) therapies are both effective for patients with relapsed/refractory (R/R) follicular lymphoma (FL), but differ in treatment schedules and associated “time toxicity,” or contact days spent physically interacting with the healthcare system. While contact days can be estimated from clinical trials, real-world data provides a more nuanced depiction of treatment-related time burden, which may guide treatment decision-making. The comparative time toxicity of CAR-T vs BsAb in R/R FL is not defined. Methods We conducted a multicenter retrospective study of adults with R/R grade 1-3A FL who received standard-of-care CAR-T (axi-cel, tisa-cel, liso-cel) or BsAb (mosunetuzumab, epcoritamab) in the third-line or later setting before Jan 1, 2025. Time toxicity was defined as outpatient or inpatient days with physical health care system contact, counting multiple visits on the same day as only one day. All days after treatment initiation were counted, regardless of disease progression, therapy completion, or relation to FL therapy. Median contact days over 1-year time horizon were compared, stratified by CAR-T vs BsAb, prior lines of therapy (LOT, 2 vs 3+), and time intervals (0-1, 1-3, 3-6, 6-9, and 9-12 months). Progression-free survival (PFS) and overall survival (OS) were calculated from day of CAR-T infusion or day 1, cycle 1 for BsAb. Cox regression and propensity matching (by age, ECOG, refractory to prior LOT, POD24) were used to assess predictors and survival associations with contact days. Results Among 209 patients from 15 U.S. academic centers, median age was 64, 37% were female, 61% received CAR-T (80% axi-cel, 7% liso-cel, 13% tisa-cel) and 39% BsAb (93% mosun, 7% epcor). Most had Grade 1-2 FL (72%), advanced stage (84%), and extranodal disease (51%). Median prior LOT was 3 (range 2-15), 41% were refractory to prior LOT, and 52% had POD24. Median number of BsAb doses was 10 (range 1-36). Patients receiving BsAb were significantly older (p<.01) and had higher CIRS comorbidity scores (p<.02) in both 2 and 3+ prior LOT cohorts, and had higher ECOG scores (p=.01) and were less likely to be refractory to prior LOT (p=.029) in 3+ LOT cohort. There were no differences in POD24 rates between CAR-T and BsAb. Median PFS for the entire cohort was 3.6 yrs; median OS was not reached. In the 2 prior LOT cohort (N=75), 60% received CAR-T and 40% BsAb. With median follow-up of 1.5 years, median PFS was not reached for CAR-T and 1.6 yrs for BsAb (p<.0001). In the 3+ prior LOT cohort (N=134), 62% received CAR-T and 38% BsAb. With median follow-up of 2 yrs, median PFS was 3.6 yrs for CAR-T and 1.6 yrs for BsAb (p=.0044). In propensity matched analysis, PFS was shorter for BsAb in both 2 LOT (HR 9.0, 95% CI 1.14-71.04, p=.037) and 3+ LOT (HR 3.25, 95% CI 1.06-9.97, p=.039) cohorts as compared to CAR-T. There were no significant differences in OS between CAR-T and BsAb. Median contact days were significantly higher for CAR-T vs BsAb in the 0-1 month interval: 19 vs 8 days in 2 LOT (p<.0001) and 18 vs 7 days in 3+ LOT (p<.0001) cohorts. There were no differences in contact days between CAR-T vs BsAb in subsequent time intervals. Over 1 year, CAR-T had significantly more time toxicity than BsAb: median 51 vs 36 contact days in 2 LOT (p<.0001) and 64 vs 38 days in 3L+ LOT (p<.0001) cohorts; these remained significant in the matched analysis. B symptoms (p=.04) and Grade ≥3 cytopenias (p=.007) were associated with higher contact days in 3+ LOT cohort in univariable analysis. Higher contact days were associated with inferior PFS (HR 1.01, 95% CI 1.00-1.02, p=.032) and OS (HR 1.01, 95% CI 1.00-1.02, p=.038) in 3+ LOT cohort regardless of treatment type. Discussion In this large real-world cohort of patients with R/R FL, CAR-T therapy resulted in better PFS but more time toxicity over the first year as compared to BsAb therapy. Excess time toxicity from CAR-T was driven by more contact days in the first month of treatment. This study provides benchmark data for counseling patients about expected time burden of CAR-T (51-64 days) and BsAb (36-38 days) over the first year of these therapies. Further, with superior PFS of CAR-T in this study and minimal impact of time toxicity on survival outcomes, these data can be used to better support shared decision-making in R/R FL by addressing patient preferences regarding both contact days as well as duration of disease control.

Abstract Epcoritamab and glofitamab are CD20-directed bispecific antibodies (BsAbs) approved in the United States for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between 1 January 2023 and 15 October 2024 were collected from 21 United States institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 2.0-3.8 months), and median overall survival (OS) was 7.8 months (95% CI, 6.2-11.0 months). The 6-month PFS was 36% (95% CI, 30-44) and the 6-month OS was 60% (95% CI, 54-67). Both trial ineligibility and undetectable CD20 pre-BsAbs portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after BsAbs with a median time to progression of 3.7 months. This analysis including patients with R/R DLBCL shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 were associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL, and underscore the importance of target antigen expression.