ALBERT

Beschreibung: Background: Aggressive non-Hodgkin lymphoma (aNHL) relapsing after high-dose therapy or, in not transplant-eligible patients, after 1st-line chemotherapy represents an unmet clinical need. Therefore, we aimed at evaluating a salvage combination regimen based on pixantrone, an aza-anthracenadione recently approved in Europe for patients with multiply relapsed aNHL. Etoposide and bendamustine were chosen as companion compounds due to available feasibility data in combination with anthracenadions, and a well-documented efficacy in salvage regimens for relapsed aNHL. Rituximab was added, if the relapse tumor biopsy was CD20+. Aim: The aim of the present analysis was to summarize the preliminary clinical experience with the PREBEN/PEBEN regimen gathered, on a compassionate need basis, at different European sites and representing the platform for a currently ongoing Nordic phase 1/2 trial in relapsed aNHL. Methods: The adopted schedule consisted of pixantrone 50 mg/m2 i.v. day 1+8, etoposide 100 mg i.v. day 1, bendamustine 90 mg i.v. day 1 with or without the addition of rituximab 375 mg/m2 i.v. day 1 (PREBEN/PEBEN). If feasible, each cycle was given at 3-weekly intervals for a maximum of 6 cycles. All patients were assessed for chemosensitivity with PET/CT, already after cycle 1 or 2. G-CSF support was applied and administered according to local practice. Results: A total of 30 heavily pre-treated patients (19 males and 11 females, age range 49-81 yrs; mean N of previous regimens: 3, range 1-7) with aNHL were treated according to the PREBEN/PEBEN schedule. Seventeen had diffuse large B-cell (DLBCL), six transformed indolent (tIND), and seven peripheral T-cell lymphoma (PTCL). All patients had intermediate or high risk IPI prior to start of salvage therapy. Eight patients (27%) had a complete metabolic response (CMR) and seven (23%) a partial one (PMR), resulting in an overall response rate (ORR) of 50%. Among the histological subtypes, the patients with DLBCL, PTCL and tIND had an ORR of 53% (CMR 35%), 57% (CMR 14%), and 33% (CMR in one out of two responders), respectively. Most responses were achieved early (prior to course nr. 4). Response durations ranged between 2 and 23+ months. Among the 17 patients with DLBCL, nine were frail, non transplant-eligible with relapsed disease, six had primary refractory lymphoma progressing through anthracycline-containing 1st line and platinum-containing salvage therapies, and two had relapses occurring after a post-transplant remission period. While most of the relapsed patients with DLBCL responded , i.e. seven (five CMR and two PMR) of the nine (78%) frail relapsed patients and one of the two (50%) patients with post-transplant relapses, only one out six (17%) primary refractory patients exhibited some chemosensitivity. Interestingly, four out of seven PTCL patients achieved a PMR or CMR allowing them to undergo non-myeloablative allogeneic transplant with subsequent sustained response durations. The treatment schedule was feasible and most patients received it on an out-patient basis. The most common grade 3-4 toxicity was of hematological type (mainly neutropenia and thrombocytopenia), occurring in 52% of the patients. Grade 3-4 infections were observed at a frequency of 21%. No septic deaths were recorded. A previously anthracycline exposed, heavily pre-treated 60-year old female PTCL patient developed symptomatic congestive heart failure effectively reversed by angiotensin converting enzyme inhibitors with normalization of the myocardial ejection fraction. One previously ibritumomab tiuxetan exposed, heavily pretreated patient with tIND developed acute myeloid leukemia with therapy-related cytogenetic features. Conclusions: The PREBEN/PEBEN salvage regimen was feasible in a heavily pre-treated cohort of elderly patients with high-risk aNHL. In individual patients it elicited substantial and durable responses early in the course of therapy. In some younger patients, it proved useful as bridging strategy to a non-myeloablative allogeneic transplant. A phase 1/2 study in relapsed (non-refractory) aNHL was launched in June 2016 (ClinicalTrial.gov identifier: NCT02678299; EudraCT number: 2015-000758-39) and is currently accruing (N=5 pr. Aug 1st, 2016). Disclosures Clausen: Takeda: Research Funding; Novartis: Other: Travel expences; Abbvie: Other: Travel expences. Leppa:Mundipharma: Research Funding; Roche: Honoraria, Other: Travel expenses, Research Funding; Bayer: Research Funding; Janssen: Research Funding; Takeda: Honoraria, Other: Travel expenses; CTI Life Sciences: Honoraria; Amgen: Research Funding; Merck: Other: Travel expenses. Willenbacher:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; European Commision: Research Funding. d'Amore:Servier: Honoraria, Other: Advisory Boards; CTI LIfe Sciences: Honoraria, Other: Advisory Boards.

Beschreibung: Background Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is an infrequent but devastating complication. The German Risk model which includes the 5 IPI risk factors plus involvement of the kidneys has been validated in 2 large independent cohorts (Schmitz, ICML 2013; Savage, ASH 2014; El-Galaly, ICML 2015). In this model, the presence of 〉1 extranodal site of involvement contributes only 1 point. However, the precise impact of the extent of extranodal disease in PET-CT staged patients is unknown. Patients and Methods We identified patients with newly diagnosed DLBCL presenting to hospitals in Denmark, Canada, the United Kingdom and Australia through systematic searches of national/local lymphoma registries. Inclusion criteria were: staging included PET-CT, primary treatment with R-CHOP or similar regimen ± CNS prophylaxis. Patients treated with high-dose regimens (such as R-HyperCVAD) and those with CNS involvement at diagnosis were excluded. Medical records and PET-CT reports were reviewed for clinical information and outcome. Multiple lesions in one organ or set of paired organs/ tissue were counted as a single extranodal site, and the spleen and Waldeyer's ring were not included as extranodal sites. Time to CNS relapse was determined using the method of Kaplan and Meier, with univariate analysis of absolute number of extranodal sites associated with CNS relapse performed using competing risk regression with death before CNS relapse as competing risk. Multivariate analyses (adjusted for elevated LDH, age〉60 y and performance status〉1) were performed using Cox proportional hazards to identify the specific increase in risk attributable to the absolute number of extranodal sites of involvement. Involvement of the kidney/adrenals and advanced disease stage were not included in the adjustment because of their intrinsic relationship to number of extranodal sites. Results 1,536 patients meeting the above criteria were included, with the following characteristics: median age 65 y (range 17-92), 63% stage III/IV, 39% B symptoms, 50% elevated LDH, 15% performance status 〉1 and 39%, 36%, 15%, 6% and 3% had 0, 1, 2, 3 and 4+ extranodal sites of involvement, respectively. 79% received no specific CNS-directed prophylaxis; 8% received intrathecal chemotherapy alone, 5% received systemic high-dose anti-metabolites and 8% received both intrathecal and systemic. After a median follow-up of 41 (interquartile range 28-61) months, 62 (4%) patients developed CNS relapse at a median of 9 (range 4-78) months from initial diagnosis. The 3-y incidence of CNS relapse, unadjusted and adjusted hazard ratios for CNS relapse according to number of extranodal sites of involvement are presented in Table 1. The competing risk regression analysis for CNS relapse using absolute number of extranodal sites of involvement is displayed in Figure 1; 〉2 vs 2 or fewer extranodal sites was associated with markedly increased risk of CNS progression (P 60 y and performance status 〉1 Number of extranodal sites n (%) 3-year incidence % (95%CI) Unadjusted hazard ratio HR (95% CI) Adjusted hazard ratio* HR (95% CI) 0 602 (39) 1.7 (0.9-3.5) 1.0 (ref) 1.0 (ref) 1 559 (36) 4.0 (2.5-6.4) 3.0 (1.3-6.7) 3.1 (1.3-7.2) 2 230 (15) 4.8 (2.4-9.4) 3.4 (1.3-8.5) 2.8 (1.0-7.5) 3 92 (6) 12.8 (6.6-24.0) 8.1 (3.1-20.9) 6.3 (2.2-17.6) 4+ 53 (3) 32.1 (20.1-48.8) 22.0 (9.0-53.6) 17.2 (6.5-45.8) Figure 1. Competing risk regression analysis depicting cumulative incidence of CNS relapse according to absolute number of extranodal sites of involvement. Figure 1. Competing risk regression analysis depicting cumulative incidence of CNS relapse according to absolute number of extranodal sites of involvement. Disclosures Hutchings: Takeda: Research Funding. Connors:Roche: Research Funding; Seattle Genetics: Research Funding. Seymour:Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Phebra: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Membership on an entity's Board of Directors or advisory committees. Villa:Roche: Research Funding.

Beschreibung: Background: Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically 1, concurrent leptomeningeal and parenchymal involvement, SCNS developing before completion of 1st line treatment, and combined systemic and CNS involvement by DLBCL were associated with inferior outcomes. Upfront CNS prophylaxis did not influence post-SCNS OS. High-dose methotrexate (HDMTX) and/or platinum based treatment regimens (i.e. ICE, DHAP, or GDP [+/- IT treatment and/or radiotherapy], N=163) for SCNS were associated with reduced risk of death (HR 0.45 [0.32-0.62, P1, and SCNS developing during first line treatment were independently associated with inferior OS. However, a significant fraction of patients with isolated SCNS after first line DLBCL treatment and with good performance status may achieve long-term remissions after intensive regimens for SCNS. Disclosures El-Galaly: Roche: Consultancy, Other: travel funding. Cheah:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Speaker's Bureau. Kansara:Celgene: Honoraria. Connors:Bristol Myers Squib: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Millennium Takeda: Research Funding; Seattle Genetics: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Opat:Roche: Consultancy, Honoraria, Other: Provision of subsidised drugs, Research Funding. Seymour:Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding.

Beschreibung: Introduction: CD20-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the treatment of B-cell non-Hodgkin lymphomas (B-NHL); however, a significant proportion of patients (pts) present with refractory disease or will experience relapse. GEN3013 (DuoBody®-CD3×CD20) is the first subcutaneously administered IgG1 bispecific antibody (bsAb) that targets the T-cell surface antigen CD3 and the B-cell surface antigen CD20, triggering T-cell-mediated killing of B cells. In vitro, GEN3013 efficiently activates and induces cytotoxic activity of CD4+ and CD8+ T cells in the presence of B cells (Hiemstra et al. Blood 2018), and results in long-lasting depletion of B cells in cynomolgus monkeys. Subcutaneous (SC) GEN3013 in cynomolgus monkeys resulted in lower plasma cytokine levels, and similar bioavailability and B-cell depletion, compared with intravenous administration. GEN3013 has higher potency in vitro than most other CD3×CD20 bsAbs in clinical development (Hiemstra et al. HemaSphere 2019). SC GEN3013 in pts with B-NHL is being evaluated in a first-in-human, Phase 1/2 trial (NCT03625037), which comprises a dose-escalation part and a dose-expansion part. Here we report preliminary dose-escalation data. Methods: Pts with CD20+ B-NHL with relapsed, progressive, or refractory disease following anti-CD20 mAb treatment, and ECOG PS 0-2 were included. During dose escalation, pts received SC GEN3013 flat dose in 28-day cycles (q1w: cycle 1-2; q2w: cycle 3-6; q4w thereafter) until disease progression or unacceptable toxicity. Risk of cytokine release syndrome (CRS) was mitigated with the use of a priming dose and premedication with corticosteroids, antihistamines, and antipyretics. Primary endpoints were adverse events (AEs) and dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics (PK), immunogenicity (anti-drug antibodies [ADA]), pharmacodynamics (PD) (cytokine measures; laboratory parameters), and anti-tumor activity (tumor size reduction; objective and best response). Results: At data cut-off (June 28, 2019), 18 pts were enrolled into the dose-escalation part of the trial, with safety data available for pts receiving doses starting at 4 µg. Most pts had diffuse large B-cell lymphoma (DLBCL; n=14) and were heavily pre-treated; 10 pts had received ≥3 prior lines of therapy (overall median [range]: 3 [1-11]). The median age was 58.5 years (range: 21-80), and 13 pts were male. At a median follow-up of 1.9 months, pts received a median of 5 doses (range: 1-14); treatment is ongoing in 6 pts. Twelve pts discontinued treatment due to progressive disease. Six pts died (2 during treatment, 4 during survival follow-up), all due to disease progression and unrelated to treatment. The most common (n≥5) treatment-emergent AEs were pyrexia (n=8), local injection-site reactions (n=7), diarrhea (n=5), fatigue (n=5), and increased aspartate aminotransferase (n=5). The most common Grade (G) 3/4 AEs were anemia (n=3) and neutropenia (n=3). Despite increasing GEN3013 doses, all CRS events were non-severe (initial observation: 3/8 pts, G1: n=1, G2: n=2; following modification of premedication plan [corticosteroids for 3 days]: 6/10 pts, G1: n=4, G2: n=2). Increases in peripheral cytokine (IL6, IL8, IL10, IFNγ, TNFα) concentrations after GEN3013 dosing correlated with clinical symptoms of CRS in most pts. No pts had tumor lysis syndrome or neurological symptoms. No DLTs were observed. GEN3013 PK profiles reflect SC dosing; Cmax occurred 2-4 days after dosing. No ADAs were detected. PD effects following GEN3013 dosing were observed at dose levels as low as 40 µg and included rapid, complete depletion of circulating B cells (if present after prior anti-CD20 therapy) and peripheral T-cell activation and expansion. The first evidence of clinical activity was observed at a dose level of 120 µg, with complete metabolic response observed in a pt with DLBCL. Conclusions: Subcutaneously administered GEN3013, a potent CD3×CD20 bsAb, shows good tolerability and early evidence of clinical activity at low dose levels in heavily pretreated pts with relapsed or refractory B-NHL. All CRS events were non-severe and did not lead to discontinuation. No DLTs were observed. Dose escalation is ongoing; updated data will be presented. Dose expansion will begin upon determining the recommended Phase 2 dose (RP2D) (NCT03625037). Disclosures Lugtenburg: Janssen Cilag: Honoraria; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria; BMS: Consultancy; Takeda: Consultancy, Honoraria, Research Funding. Mous:Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Sandoz: Honoraria; Roche: Honoraria; Abbvie: Honoraria; Takeda: Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; MSD: Honoraria; Gilead: Consultancy, Honoraria, Research Funding. Clausen:Abbvie: Other: Travel grant to attend ASH 2019. Johnson:Boehringer Ingelheim: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria; Epizyme: Honoraria, Research Funding; Incyte: Honoraria; Takeda: Honoraria; Genmab: Honoraria; Bristol-Myers Squibb: Honoraria; Kite: Honoraria; Novartis: Honoraria. Rule:Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Napp: Consultancy; Kite: Consultancy. Oliveri:Genmab: Employment, Equity Ownership. DeMarco:Genmab: Employment, Equity Ownership. Hiemstra:Genmab: Employment, Equity Ownership, Other: Warrants. Chen:Genmab: Employment. Azaryan:Genmab: Employment. Gupta:Genmab: Employment, Equity Ownership. Ahmadi:Genmab Inc: Employment, Other: stock and/or warrants. Hutchings:Incyte: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Janssen: Research Funding; Pfizer: Research Funding.

Beschreibung: Introduction: In Denmark, as in most other Western countries, follicular Lymphoma (FL) is the second most common lymphoma entity. Although still regarded as an incurable condition, FL is characterized by an indolent clinical course, a natural history of recurrent relapses and in some cases transformation to an aggressive histology (HT). The addition of the anti CD20 antibody Rituximab to chemotherapy (r-chemo) has had a profoundly favorable impact on the time to relapse, survival and possibly also transformation rates (N. Wagner-Johnston et al, Blood, 2015; C. Sarkozy et al, JCO, 2016). During the last decade maintenance with Rituximab after initial immuno-chemotherapy, has been introduced with the hopes of further improving outcome for patients with FL. Aims: In this population-based study of real world data, we investigated the effect of upfront Rituximab maintenance (RM) on progression, survival and HT in FL patients. Patients and Methods: Patients diagnosed with histologically verified FL or Diffuse Large B-cell Lymphoma (DLBCL) in Denmark from 2000-2015 were identified through the National Danish Pathology Registry. Pathology reports were reviewed for patients diagnosed with both FL and DLBCL during the study period. HT was defined as initial biopsy proven FL diagnosis followed, in the same patient, by a subsequent biopsy-verified FL grade 3B or DLBCL. The identified patient cohort was cross-linked with the Danish Lymphoma Registry (LYFO). From this population, patients were included if meeting the following criteria: (i) completed first-line induction treatment with r-chemo, (ii) alive and eligible for RM at the time of clinical evaluation after induction treatment, and (iii) no evidence of HT at the same time point. Decision of treatment-free follow up or RM was applied according to local guidelines (RM was introduced at different time-points at different lymphoma-treating tertiary centers in Denmark). The RM-schedule consisted of 375 mg/m2 intravenous or subcutaneous every other month for 2 years. Statistical methods: Patient characteristics were compared using Fisher's exact or Student's t test. All time related end-points were estimated by Kaplan-Meier time-to-event analyses and compared using the log-rank test. Overall survival (OS) was defined from the date of FL diagnosis to the date of death by any cause or censoring; Progression-free survival (PFS) was calculated from the date of FL diagnosis to the date of progression/relapse or censoring. Time-to-transformation (TTT) was calculated from the date of FL-diagnosis to the date of biopsy proven HT. Factors of potential clinical relevance were tested in a multivariate analysis using a Cox proportional Hazards model. Results: 722 patients had completed their first Rituximab-containing induction treatment; 364 patients were consolidated with RM while 358 were not. The two treatment cohorts (no-RM vs. RM) were comparable in terms of sex and age distribution as well as performance score and LDH-elevation. Patients receiving RM had more often advanced Ann Arbor stage (p

Beschreibung: Introduction: Despite advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL), more efficacious, less toxic, off-the-shelf therapies are needed for patients (pts) with relapsed or refractory (R/R) disease. Epcoritamab is a novel, subcutaneously (SC) administered bispecific antibody (bsAb) that simultaneously binds to CD3 on T cells and CD20 on B cells, inducing activation and cytotoxic activity of T cells for killing of target lymphoma cells. In an open-label, phase 1/2 trial (NCT03625037), initial data demonstrated an encouraging safety profile and potent single-agent clinical activity, even at low doses, in heavily pretreated pts with R/R B-NHL (Hutchings M. EHA 2020, Poster EP1218). Herein, we present updated dose-escalation data, including initial results for the 48-mg recommended phase 2 dose (RP2D) and for pts with mantle cell lymphoma (MCL). Methods: Adults with R/R CD20+ B-NHL after prior therapy, including an anti-CD20 monoclonal antibody (mAb), receive a SC 1-mL injection of flat-dose epcoritamab in 28-day cycles (q1w: cycles 1-2; q2w: cycles 3-6; q4w thereafter) until disease progression or unacceptable toxicity. Risk mitigation for cytokine release syndrome (CRS) includes starting with priming and intermediate doses and use of corticosteroids. Objectives include dose finding, safety, and antitumor activity. Results: As of July 6, 2020, 67 pts were enrolled, which included 45 pts (67%) with diffuse large B-cell lymphoma (DLBCL), 12 (18%) with follicular lymphoma (FL) and 4 (6%) with MCL. Pts were heavily pretreated, with a median (range) of 3.0 (1-6) prior lines of therapy for pts with DLBCL and 4.5 (1-18) for pts with FL; in total 6 pts had received prior CAR-T therapy. Over one-half of pts (37/67; 55%) were refractory to their most recent systemic therapy; 35/67 (52%) were refractory to their most recent anti-CD20 mAb therapy. At a median overall follow-up of 8.3 months, treatment is ongoing in 25 pts (37%); median follow-up is 8.3 months for pts with DLBCL and 8.8 months for pts with FL. Epcoritamab was well tolerated and there were no discontinuations due to treatment-related adverse events (AEs). The most common treatment-emergent AEs (TEAEs) were pyrexia (70%), local injection-site reactions (48%), and fatigue (45%). With increased doses, TEAEs of special interest were consistent with previous reports: CRS events were all grade 1/2 (58%) with no grade 3/4 CRS events, and limited neurotoxicity was observed (6%; grade 1: 3%; grade 3: 3%; all transient). There were no dose-limiting toxicities or febrile neutropenia events, and no deaths due to treatment-related AEs. Antitumor activity in evaluable pts with DLBCL and FL is shown in the Table. In 18 pts with DLBCL receiving epcoritamab ≥12 mg, overall response rate (ORR) was 66.7% with 6 pts achieving a complete response (CR). Of the 7 pts who received epcoritamab ≥48 mg (48-mg RP2D n=4; 60-mg n=3), all achieved a response, including CR in 2 pts (28.6%) with limited follow-up. All pts with DLBCL who were previously treated with CAR-T therapy achieved a response (4/4: 2 CR, 2 partial response [PR]). ORR was 100% for the 8 pts with FL receiving epcoritamab ≥0.76 mg, with 2 pts achieving a CR (PET scans were not mandatory and disease assessment by PET was not available in 4/6 pts who achieved a PR). Of the 4 pts with MCL, responses have been observed in 2 pts with blastoid variant MCL (1 CR; 1 PR). Data on duration of response are not yet mature. Longer follow-up data, including additional response evaluations at 48-mg dose and in pts with MCL, will be presented. Conclusions: Epcoritamab, a novel SC bsAb, demonstrates a consistent and favorable safety profile, with no grade ≥3 CRS events and limited neurotoxicity, in support of outpatient administration. Emerging data with longer follow-up are highly encouraging, with substantial single-agent efficacy, including CR in heavily pretreated pts with FL, MCL, and DLBCL. Study support: Genmab A/S. Medical writing: Alyson Bexfield, Caudex, UK, funded by Genmab A/S. Disclosures Hutchings: Celgene, Genmab, Janssen, Novartis, F. Hoffmann-La Roche, Takeda: Research Funding; Genmab, F. Hoffmann-La Roche, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Mous:Gilead Sciences: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Sandoz: Honoraria; Takeda: Honoraria; MSD Brazil: Honoraria; Roche: Honoraria; AbbVie: Honoraria. Clausen:AbbVie: Other: Travel expenses. Johnson:Incyte: Honoraria; Kite Pharma: Honoraria; Kymera: Honoraria; MorphoSys: Honoraria; Takeda: Honoraria; Genmab: Honoraria; Celgene: Honoraria; Bristol-Myers: Honoraria; Oncimmune: Consultancy; Janssen: Consultancy; Oncimmune: Consultancy; Epizyme: Consultancy, Research Funding; Janssen: Consultancy; Boehringer Ingelheim: Consultancy; Epizyme: Consultancy, Research Funding; Novartis: Honoraria. Linton:Takeda: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Travel, accommodations, expenses ; Celgene: Other: Travel, accommodations, expenses. Chamuleau:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Genmab: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sureda Balari:Gilead/Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Speakers Bureau; Celgene: Consultancy, Honoraria; Incyte: Consultancy; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria. Cunningham:Bayer: Research Funding; AstraZeneca: Research Funding; Merrimack: Research Funding; Celgene: Research Funding; Amgen: Research Funding; Merck: Research Funding; Sanofi: Research Funding; MedImmune: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees; Lilly: Research Funding; Janssen: Research Funding; Clovis Oncology: Research Funding; 4SC: Research Funding. Oliveri:Genmab: Current Employment, Current equity holder in publicly-traded company. DeMarco:Genmab: Current Employment, Current equity holder in publicly-traded company. Elliott:Genmab: Current Employment. Chen:Genmab: Current Employment. Lugtenburg:Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Roche: Research Funding; Genentech: Honoraria; Genmab: Honoraria; Celgene: Honoraria; Incyte: Honoraria. OffLabel Disclosure: Epcoritamab is an investigational agent undergoing evaluation in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.