Moustafa, Magda

e19095 Background: Richter transformation (RT), the progression of chronic lymphocytic leukemia to aggressive diffuse large B-cell lymphoma, carries poor outcomes. Chemoimmunotherapy (CIT), including R-CHOP, remains commonly used in the frontline setting, while CD19-directed CAR T-cell therapy is used mainly in relapsed/refractory (R/R) disease but is limited by toxicity and access. CD3×CD20-targeting bispecific antibodies (BsAbs) are off-the-shelf immunotherapies with emerging prospective data in RT. We systematically evaluated the efficacy and safety of BsAbs across treatment lines. Methods: We did a systematic search on PubMed, Google Scholar, and ClinicalTrials.gov. Updated studies of four trials met the inclusion criteria. Outcomes were stratified by line of therapy (first-line [1L] vs relapsed/refractory [R/R]) and regimen (monotherapy vs combination). Primary endpoints were overall response rate (ORR) and complete response (CR) per Lugano 2014 criteria. Cytokine release syndrome (CRS) was graded per ASTCT criteria. Results: A total of 138 patients were evaluated (97 monotherapy, 41 combination). In the 1L setting (n=21), epcoritamab monotherapy achieved an ORR of 57% and CR rate of 52%, with an mOS of 27.5 months, more than doubling historical CIT (R-CHOP) survival (<12 months). In R/R RT, mosunetuzumab (n=20) and glofitamab (n=11) demonstrated ORRs of 40% and 63.6% with CR rates of 20% and 45.5%, respectively. The BLINART study with Blinatumomab (n=25) reported an ORR of 46% and CR of 20%. Combination regimens (n=41) showed favorable responses similar to those reported with CD19-directed CAR T-cell therapy in multicenter registries, though cross-trial comparisons are limited: epcoritamab plus lenalidomide achieved a CR rate of 73%, and epcoritamab plus R-CHOP achieved a CR of 60%. Grade ≥3 CRS occurred in <9% of patients, lower than rates reported with CAR T-cell therapy (16%). Neutropenia was the most common grade ≥3 adverse event. Conclusions: CD3×CD20 bispecific antibodies demonstrate meaningful clinical activity in RT, with signals of improved frontline survival versus historical CIT and favorable efficacy and safety across R/R settings. More data from clinical trials is needed to establish clear superiority. Prospective CD3×CD20 BsAb trials in RT and comparison with R-CHOP and CAR T cell therapy. Trial / Regimen Population N ORR (%) CR (%) mOS Gr ≥3 CRS Epcoritamab + Lena R/R 11 82.0% 73.0% NR 9.0% Epcoritamab + R-CHOP R/R 30 73.0% 60.0% 16.4 mo 3.0% Epcoritamab Mono 1L 21 57.1% 52.0% 27.5 mo 7.0% Glofitamab Mono R/R 11 63.6% 45.5% NR 0.0% Mosunetuzumab Mono R/R 20 38.1% 29.0% 9.8 mo 7.0% Epcoritamab Mono R/R 20 40.0% 20.0% 11.4 mo 5.0% Blinatumomab (Seq) R/R 25 36.0% 20.0% NR 8.0% CIBMTR (CAR-T Ref) R/R 140 — — 46.6% (2-yr OS) — Kittai et al. (CAR-T Ref) 1L 69 63.0% 46.0% 8.5 mo 16.0% R-CHOP (CIT Ref) 1L — 40–60% 20.0% 6–12 mo 0.0%

e13677 Background: The development of AI led to the emergence of tools such as AIS, which have been increasingly adopted in medicine. However, formal evaluation of barriers and clinical care gaps in HemOnc is limited, particularly regarding treatment plan complexities and toxicity documentation. Methods: Structured investigator-developed surveys about AIS availability, adoption, benefits, and challenges were developed on Qualtrics and approved by the IRB. HemOnc faculty physicians (FP), advanced practice providers (APP), and trainees (HOT) were surveyed between 11/14/25-1/16/26. Surveys were distributed in the USA via email, social media (on X), and ASCO myConnection. Descriptive statistics were used for analysis. Results: 132 participants responded to the survey: 55 FP (42%), 14 APP (11%), and 63 HOT (48%). 80% of them reported having AIS at their institutions, and 54% of those reported using these tools in their clinical practice. Among FP and APP, 72% practiced in academic settings, 14% in community, and 13% in hybrid centers. Among those not using AIS, identified barriers were issues with note formatting (56%), lack of training (25%), and concerns that the note content is incorrect or inadequate (25%). 60% are willing to use AIS if note formatting matched their preference, and 42% would try it if contents better reflected the patient encounter. Table 1 details the proportion of encounters using AIS, the portion of documentation it was used for, and the perceived challenges with these tools. Among AIS users, the average satisfaction score was 5.3 on a 7 point scale, corresponding to participants being somewhat satisfied. Participants agreed slightly that AIS had reduced their feeling of work-related burnout, with an average score of 3.6 on a 5 point scale. Overall, participants felt neutral about how well-suited AIS are for HemOnc, with an average score of 4.0 on a 7 point scale. Conclusions: Despite AIS being widely available, 46% of the surveyed HemOnc workforce do not use them in clinical practice. Those who do reported decreased time spent on documentation outside work hours and a slight reduction in the feeling of burnout. Formatting issues and record integration remain barriers, with substantial concerns about AIS not adequately describing HemOnc treatment plans. To bridge the last mile of integration into HemOnc, partnership between AIS developers and the clinical workforce is essential to meet clinical needs, while prioritizing patient safety and data privacy. FP + APP % HOT % Patient encounters where AIS is used 62 44 Used AIS for the subjective portion of note 68 96 Used AIS for the assessment/plan portions of note 40 25 AIS decreased the time on clinical documentation outside work hours 96 93 AIS note formatting needs improvement 68 57 Issues integrating AIS and outside records 46 71 AIS note contents about the plan are suboptimal 32 61

7011 Background: Up to 40% of pts with diffuse large B-cell lymphoma (DLBCL) will relapse or have refractory disease following 1L treatment (Tx) with SOC chemoimmunotherapy regimens R-CHOP or Pola-RCHP. High risk (HR) populations include those with International Prognostic Index (IPI) score 3–5 and IPI 1–2 with either ≥1 lesion ≥7 cm or baseline LDH >1.3×ULN. GOLCA is a potential, first-in-class, oral CELMoD designed for the Tx of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA 0.4 mg + R-CHOP has shown promising safety, a ≥90% minimal residual disease (MRD) negativity rate, and durable efficacy (24-mo PFS, 79%) in 1L a-BCL (Nowakowski et al, ASH 2025, 476) and is being evaluated in the Phase (Ph) 3 study GOLSEEK-1 (NCT06356129). We report initial Ph1b results with GOLCA + Pola-RCHP in 1L a-BCL. Methods: Pts aged ≥18 y with ECOG PS ≤2, IPI 0–5 (Part 2A) or 2–5 (Part 2B), and newly diagnosed a-BCL with measurable tumorous disease were included. Pts were treated with GOLCA + Pola-RCHP for six 21-day (D) cycles or until disease progression/unacceptable toxicity/study withdrawal. In dose escalation, GOLCA was dosed at 0.2 and 0.4 mg D1–7. In dose expansion, pts were randomized 1:1 to Pola-RCHP + GOLCA 0.2 or 0.4 mg. Primary endpoint: safety; efficacy was a secondary endpoint. Results: At data cutoff, 57 pts were treated with GOLCA + Pola-RCHP (0.2 mg, n=28; 0.4 mg, n=29). Median age was 63 y. Most pts had HR disease (86%) and DLBCL not otherwise specified histology (84%). For known cell of origin (COO), 47% were germinal center B cell (GCB) and 39% non-GCB by Hans algorithm. Forty-seven pts (83%) completed Tx and 52 (91%) entered the follow-up (f/u) period. Grade 3/4 Tx-emergent adverse events occurred in 95% of pts, most frequently neutropenia (86%; an on-target side effect of GOLCA) and anemia (39%). Median relative dose intensity for GOLCA and Pola-RCHP components was >95%. At 15.5 mo median f/u, end of Tx (EOT) complete metabolic response (CMR) rate was 69% at 0.2 mg, 82% at 0.4 mg, and similar across COO subtypes. EOT CMR was consistent in HR pts (65% at 0.2 mg, 83% at 0.4 mg). The 12-mo DOR and PFS rates were 92% and 88% at 0.2 mg, and 96% and 96% at 0.4 mg. In pts with both pre-Tx and EOT ctDNA analysis, 65% and 83% at 0.2 and 0.4 mg achieved MRD negativity (PhasED-Seq) at EOT. Conclusions: GOLCA + Pola-RCHP demonstrated a predictable and manageable safety profile, and addition of GOLCA did not compromise median dose intensity of Pola-RCHP. GOLCA 0.4 mg + Pola-RCHP resulted in a high rate of durable CMRs, high rate of MRD negativity, and a promising 12-mo PFS rate. These data continue to show that GOLCA + SOC regimens R-CHOP and Pola-RCHP has potential to improve outcomes in 1L HR a-BCL. Clinical trial information: NCT04884035 .