Mun, Yong

7029 Background: Mosun, a CD20xCD3 T-cell engaging bispecific antibody, is approved for relapsed/refractory follicular lymphoma after ≥2 prior lines of therapy. We report an interim analysis and PROs with Mosun SC in elderly/unfit patients with previously untreated DLBCL. Methods: MorningSun (NCT05207670) is a Phase 2, basket study of Mosun SC in patients with B-cell non-Hodgkin lymphoma. In the DLBCL cohort, eligible patients (aged ≥80 years, or 65–79 years and ineligible for chemoimmunotherapy) received outpatient Mosun SC: Day (D) 1 (5 mg), D8 (45 mg) and D15 (45 mg) of Cycle (C) 1, then 45 mg on D1 for up to 17 21-day cycles. Primary endpoint was progression-free survival (PFS) rate at 24 months. Other endpoints included overall survival (OS), objective response rate (ORR), complete response (CR) rate, change from baseline (CfB) in lymphoma symptoms as assessed by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LYMS; higher scores indicate improvement, a ≥3-point increase is considered clinically meaningful) and safety. Results: Forty-nine patients were enrolled, primarily from community sites (n=34). Median age was 83 years (range: 71–101). International Prognostic Index was 3–5 in 53.1% patients and 18.4% of patients had bulky disease. As of February 10, 2025, the median duration of follow-up was 12.5 months (range: 1.4–30.8). PFS and OS rates at 12 months were 71.3% (95% confidence interval [CI]: 54.8–82.7) and 74.7% (95% CI: 58.5–85.4), respectively. ORR was 73.5% and CR rate was 59.2%. Completion rates for FACT-Lym LYMS were ≥95% at baseline and remained ≥87% at each subsequent timepoint. Patients reported improvement in health-related quality of life (HRQoL) over time, demonstrated by increased mean CfB (standard deviation [SD]) in FACT-Lym LYMS scores: C4D1, 5.1 (9.8); C9D1, 5.6 (11.8); C17D1, 9.8 (11.4). Clinically meaningful improvements in lymphoma symptoms were observed in 53.1% (95% CI: 38.3–67.5) of patients. The most common any-grade adverse event (AE) was injection site reaction (53.1%; all Grade [Gr] 1/2). Gr 3/4 AEs were reported in 65.3% of patients and 8.2% experienced a Gr 5 AE (no Gr 5 AEs were Mosun related, per investigator assessment). Serious AEs occurred in 42.9% of patients. Infection AEs occurred in 49.0% of patients (Gr 1: 4.1%; Gr 2: 28.6%; Gr 3: 16.3%) and resolved in 91.7%. Cytokine release syndrome occurred in 12.2% of patients (Gr 1: 10.2%; Gr 2: 2.0%; all resolved). Updated data with around one additional year of follow-up will be presented. Conclusions: Mosun SC showed promising efficacy with manageable safety in elderly/unfit patients with previously untreated DLBCL in an outpatient setting. Clinically meaningful improvements in lymphoma symptoms suggest that Mosun SC improves aspects of HRQoL in this population. Clinical trial information: NCT05207670 .

Abstract Background: Mosunetuzumab, a CD20xCD3 bispecific antibody, can be administered in the outpatient setting for a fixed duration. Mosunetuzumab by intravenous (IV) administration is FDA- and EMA-approved in relapsed/refractory (R/R) FL after ≥2 prior lines of therapy. Interim results from the Phase II MorningSun study (NCT05207670) demonstrated promising efficacy and manageable safety of mosunetuzumab SC in pts with previously untreated HTB FL (Flinn et al. ASCO 2025). We report 12-month follow-up efficacy and safety data of mosunetuzumab SC in pts with previously untreated HTB FL in the MorningSun study, including pts who received optional maintenance therapy. Methods: Pts with previously untreated HTB FL, per Groupe D'Etude des Lymphomes Folliculaires criteria, and Eastern Cooperative Oncology Group performance status of 0–2 were enrolled, primarily from United States (US) community sites. Mosunetuzumab SC was administered as step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) followed by 45mg on D1 of each 21-day cycle, for up to 17 cycles (1 year). Pts with a partial or complete metabolic response (CMR) after C17 could receive optional mosunetuzumab maintenance treatment (45mg every 8 weeks for up to 1 year). The primary endpoint was progression-free survival (PFS) rate at 1 year. Key secondary endpoints included objective response rate (ORR), duration of response (DOR), duration of complete response (DOCR) and safety. Exploratory analysis of ctDNA levels was performed using the AOA-NHL assay. Results: As of February 10, 2025, 103 pts were enrolled (n=82 pts from community sites, n=21 pts from academic sites). Overall, the median age was 65 years (range: 24–86), 51.5% of pts were female and most pts had Ann Arbor stage III/IV disease (91.3%) and a FLIPI score ≥2 (78.6%). In total, 69 pts completed initial treatment (17 cycles), 33 discontinued (primarily due to progressive disease [PD; n=18] and adverse events [AEs; n=5]), and 1 pt was continuing treatment. After 17 cycles, 68 pts were eligible for maintenance treatment, of whom 46 received maintenance, and 15 were continuing maintenance treatment at the time of data cut-off. Median duration of follow-up was 22.3 months (95% confidence interval [CI]: 20.9–24.1). The 12-month PFS rate was 85.5% (95% CI: 76.2–91.3). The ORR was 87.4% (95% CI: 79.4–93.1); 64.1% of pts had a CMR. The 12-month OS rate was 91.9% (95% CI: 84.5–95.9); the 12-month DOR and DOCR rates were 89.6% (95% CI: 80.2–94.7) and 91.1% (95% CI: 79.4–96.2), respectively. Of the 46 pts who received maintenance, no pts experienced PD, and 1 pt died (reason unknown). Of the 22 pts who were eligible but did not receive maintenance, 1 pt had PD. The most common AEs (≥30%) were injection-site reaction (67.0%), fatigue (44.7%), cytokine release syndrome ([CRS] 34.0%), headache (32.0%), and nausea (32.0%). Grade (Gr) ≥3 AEs and serious AEs were reported in 47.6% and 35.9% of pts, respectively. Five pts experienced Gr 5 AEs: COVID-19 pneumonia (n=2) and cardiogenic shock, unexplained death, pneumonia (n=1 each). Infections occurred in 77.7% of pts and were predominantly Gr 1/2 (Gr 1: 10.7%; Gr 2: 47.6%; Gr 3: 12.6%; Gr 4: 3.9%), with the most common infection being COVID-19 (24.3%). Of 3 (2.9%) Gr 5 infections reported, 1 occurred during initial treatment (COVID-19), 1 during maintenance (pneumonia), and 1 occurred 2.8 months after completion of treatment (COVID-19). AEs were reported in 80.4% of pts in the maintenance phase, mostly Gr 1/2 events. No CRS events occurred during maintenance treatment. Infections were reported in 45.7% of pts during maintenance, with the majority being Gr 1/2 events (37.0%), and were similar types of infection as during initial therapy. ctDNA levels were assessed in a subset of pts who achieved a CMR; 86.4% (19/22) of pts were minimal residual disease (MRD) negative (p-value cut-off 0.005).Conclusions: Longer follow-up of mosunetuzumab SC with optional maintenance treatment continues to demonstrate promising PFS and OS rates, and a manageable safety profile in pts with previously untreated HTB FL. Exploratory analysis of ctDNA in a subset of CMR pts showed MRD negativity in 86.4%, thus supporting fixed treatment duration of mosunetuzumab SC. Overall, these data support the outpatient administration of mosunetuzumab SC in US community practices and further evaluation of mosunetuzumab-based treatment in first-line HTB FL.

Abstract Background: Mosunetuzumab (Mosun) is an off-the-shelf, CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells, including those that cause malignant disease. Mosun is FDA- and EMA-approved for relapsed/refractory follicular lymphoma (FL) after ≥2 prior lines of therapy as a fixed-duration intravenous treatment, and can be given in an outpatient setting without mandatory hospitalization. Initial Phase I/II data with Mosun monotherapy have shown notable efficacy and manageable safety in patients with previously untreated diffuse large B-cell lymphoma (DLBCL; NCT03677154; Olszewski et al. ASH 2022). The Phase II MorningSun study is the first to assess the efficacy and safety of subcutaneous (SC) Mosun monotherapy in elderly/unfit patients with previously untreated DLBCL; we report an interim analysis for this study. Methods: MorningSun (NCT05207670) is an open-label, multicenter, Phase II, basket study evaluating the safety, efficacy, and pharmacokinetics of Mosun SC monotherapy in patients with B-cell non-Hodgkin lymphoma. In the DLBCL cohort, eligible patients aged ≥80 years or aged 65–79 and considered ineligible for chemoimmunotherapy (CIT) were enrolled, primarily in US community sites. Hospitalization was not mandatory. Step-up doses of Mosun SC were administered on Day (D) 1 (5mg), D8 (45mg) and D15 (45mg) of Cycle 1, followed by 45mg on D1 of 21-day cycles, for up to 17 cycles or until unacceptable toxicity. The primary endpoint in this cohort was progression-free survival (PFS) rate at 24 months after first study treatment. Secondary endpoints included objective response rate (ORR), complete response (CR) rate, time to response (TTR), duration of response (DOR), duration of complete response (DOCR), overall survival (OS), and safety. An exploratory circulating tumor DNA analysis was performed using an AOA-NHL assay. Results: Overall,49 patients were enrolled, the majority at community sites (community, n=34; academic, n=15). Thirty-six patients had DLBCL, 6 had high-grade [Gr] B-cell lymphoma, 2 had T-cell/histiocyte-rich large B-cell lymphoma, and 1 had Gr 3B FL (histology missing/other lymphoma, n=4). Median age was 82.5 years (range: 71–101); 63.3% and 20.4% of patients had an ECOG performance status of 1 and 2, respectively; 40.8% had Ann Arbor stage IV disease; 51.0% had extranodal involvement; 18.4% had bulky disease; and 53.1% had an IPI score of 3–5. At the clinical cut-off date of February 10, 2025, 23 (46.9%) patients had discontinued treatment, mainly due to progressive disease (n=12, 24.5%) or an adverse event (AE; n=5, 10.2%); the median duration of follow-up was 12.5 months (range: 1.4–30.8) and the median number of cycles received was 14 (range: 1–17). The PFS rate at 12 months was 68.8% (95% confidence interval [CI]: 52.1–80.6) and OS rate at 12 months was 77.2% (95% CI: 61.1–87.3). The ORR and CR rates were 73.5% and 59.2%, respectively. Median TTR was 2.7 (range: 2.5–6.1) months. DOR and DOCR rates at 12 months were 84.6% (95% CI: 66.8–93.3) and 95.0% (95% CI: 69.5–99.3), respectively. The most common AE (any grade) was injection site reaction (n=25, 51.0%), which was mostly Gr 1 (n=24, 49.0%). Gr 3/4 AEs occurred in 65.3% (n=32) of patients, most commonly infections (16.3% [n=8]) and decreased neutrophil count (10.2% [n=5]); serious AEs occurred in 42.9% (n=21) of patients. Four patients experienced Gr 5 AEs (congestive cardiac failure, volvulus, unexplained death and intracranial hemorrhage, n=1 each); none were related to Mosun per investigator assessment. Infections occurred in 46.9% (n=23) of patients (Gr 1/2, 30.6% [n=15]; Gr 3, 16.3% [n=8]); no Gr 4/5 infections were observed. No immune effector cell-associated neurotoxicity syndrome events occurred. Cytokine release syndrome was reported in 12.2% (n=6) of patients, with 10.2% (n=5) Gr 1 and 2.0% (n=1) Gr 2 events, all of which resolved. In evaluable patients with a CR (n=16), 68.8% (n=11) of patients were minimal residual disease negative (p-value cut-off 0.005).Conclusions: There remains an unmet need for effective chemotherapy-free options in previously untreated elderly and CIT-ineligible patients with DLBCL. Interim data from MorningSun demonstrate that fixed-duration Mosun SC monotherapy is active in these patients, with promising efficacy and a manageable safety profile, with predominantly mild-to-moderate AEs, allowing for outpatient administration in the community practice setting.

Abstract Background: There remains an opportunity for new therapies to improve long-term outcomes for patients with low-tumor burden follicular lymphoma (FL). Mosunetuzumab is an off-the-shelf CD20xCD3 bispecific antibody, approved as an intravenous therapy for patients with relapsed/refractory FL after ≥2 lines of systemic therapy. Mosunetuzumab can be administered in the outpatient setting as a fixed-duration regimen. In an open-label, multicenter, Phase II study conducted mainly across US community sites (MorningSun; NCT05207670), mosunetuzumab administered subcutaneously (SC) induced high response rates with a manageable safety profile in patients with previously untreated low-tumor burden FL (Burke et al. ASH 2024). Here we present updated efficacy and safety data for mosunetuzumab SC in patients with previously untreated, low-tumor burden FL. Methods: Patients had untreated Grade 1 or 2 low-tumor burden FL per Groupe d'Etude des Lymphomes Folliculaires criteria, Ann Arbor stage III/IV disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2. Mosunetuzumab SC was administered with step-up dosing in Cycle 1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg), then 45mg on D1 of each 21-day cycle. Hospitalization was not mandatory. Patients with a complete metabolic response after 8 cycles could complete therapy and patients with a partial metabolic response or stable disease continued treatment for up to 17 cycles. The primary endpoint was progression-free survival (PFS) at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), duration of response (DOR), duration of complete response (DOCR), and safety. Exploratory analyses assessed pharmacodynamic changes in B-cell subsets. Here, we report interim data. Results: As of February 10, 2025 (clinical cut-off date), 101 patients were enrolled from US community (n=56) and academic (n=45) centers; 52 patients had completed treatment, 21 had discontinued (mainly due to adverse events [AEs; n=6] and progressive disease [n=5]), and 28 were ongoing on treatment. Median age was 65 years (range: 34–82). Most patients had an ECOG PS of 0 (81.2%) or 1 (18.8%) and 43 patients (42.6%) had extranodal involvement. Median duration of follow-up was 13.8 months (95% confidence interval [CI]: 11.5–16.9) and median number of cycles received was 10 (range: 3–17). The ORR was 98.0% (95% CI: 93.0–99.8) and the complete response rate was 89.1% (95% CI: 81.3–94.4). Median TTR was 2.8 months (range: 1.4–8.3). Landmark DOR and DOCR rates at 12 months were 91.8% (95% CI: 81.5–96.5) and 95.7% (95% CI: 82.6–99.0), respectively. The 12-month PFS and OS rates were 92.0% (95% CI: 83.8‒96.1) and 99.0% (95% CI: 93.2‒99.9), respectively. The most common AE was injection-site reaction (ISR, 81.2%; Grade 1, 74.3%; Grade 2, 5.9%; Grade 3, 1.0%). Grade 3/4 AEs were reported in 51.5% of patients; the most common (≥10%) events were cytopenias (36.6%) and infections (11.9%). Cytokine release syndrome (CRS) was reported in 48.5% of patients (Grade 1, 40.6%; Grade 2, 7.9%). Overall,infections occurred in 63.4% of patients (Grade 1, 7.9%; Grade 2, 42.6%; Grade 3, 11.9%; Grade 5, 1.0%) with the most common (≥10%) being upper respiratory tract infection (21.8%), COVID-19 (17.8%), sinusitis (13.9%), and pneumonia (11.9%). At the time of data cut-off, ISR, CRS, and infection AEs were resolved at rates of 98.2%, 100%, and 89.0%, respectively. Two patients had a Grade 5 AE (sepsis, n=1; unknown cause, n=1).No immune effector cell-associated neurotoxicity syndrome events were reported. B-cell depletion was observed following the first dose of mosunetuzumab, with subsequent B-cell recovery observed within six months of treatment completion. Conclusions: Fixed-duration mosunetuzumab SC demonstrates high efficacy rates with deep and sustained responses in patients with previously untreated, low-tumor burden FL. The manageable safety profile supports ease of outpatient administration without mandatory hospitalization, including in community oncology practices. Additionally, exploratory analyses demonstrating B-cell recovery after treatment completion also substantiate the use of mosunetuzumab SC as a fixed-duration regimen. These data support further evaluation of mosunetuzumab SC in patients with previously untreated, low-tumor burden FL.

7014 Background: Mosun is a CD20xCD3 bispecific antibody that can be administered in the outpatient setting for a fixed duration. Intravenous Mosun is approved for the treatment of relapsed/refractory FL after ≥2 prior lines of therapy. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We report the efficacy and safety of Mosun SC in patients with previously untreated high-tumor burden FL in the Phase II MorningSun study (NCT05207670). Methods: Patients with previously untreated high-tumor burden FL, per GELF criteria, were enrolled into this cohort. Mosun SC was administered with step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) then 45mg on D1 for up to 17 cycles (1 year; 21-day cycles). Patients with a partial or complete metabolic response (CMR) after C17 could receive additional Mosun maintenance therapy (45mg every 8 weeks for up to 1 year). Corticosteroid prophylaxis to reduce the risk of cytokine release syndrome (CRS) was mandatory in C1–2 and optional thereafter. The primary endpoint was progression-free survival (PFS) rate at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), and safety. Results: As of May 29, 2024, 102 patients were enrolled; 55 patients had completed initial treatment (17 cycles), 31 had discontinued (most commonly due to progressive disease [n=19] and adverse events [AEs; n=4]), and 16 were ongoing initial treatment. Forty-two patients received maintenance treatment, and this was ongoing in 38 patients. Median age was 65 years (range: 24–86); 52.0% of patients were female. Most patients had Ann Arbor stage III/IV (91.2%) and a FLIPI score ≥2 (78.4%). Median duration of follow-up was 13.9 months. The 12-month PFS rate was 82.8% (95% confidence interval [CI]: 73.0–89.3). ORR was 87.3%; 60.8% of patients had a CMR. Among the 89 patients with a response, the median TTR was 2.7 months (range: 1.2–5.8). The most common AEs (≥30%) were injection-site reaction (57.8%), fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 AEs and serious AEs (SAEs) were reported in 44.1% and 29.4% of patients, respectively. CRS events were all Grade 1/2 and SAE of CRS occurred in 10.8% of patients (Table); all events resolved. Conclusions: Mosun SC demonstrated promising efficacy in patients with previously untreated high-tumor burden FL. The manageable safety profile, including rate of CRS, supports the administration of fixed duration Mosun SC in an outpatient setting. Additional data, including cytokine profiling and T/B/NK dynamics, will be presented. Clinical trial information: NCT05207670 . CRS events, n (%) PatientsN=102 Any grade 35 (34.3) Grade12 30 (29.4)5 (4.9) SAE 11 (10.8) ManagementSteroidsTocilizumabSteroids + tocilizumabFluidsICU admission 8 (7.8)6 (5.9)3 (2.9)3 (2.9)2 (2.0)

ABSTRACT Rituximab, gemcitabine, and oxaliplatin (R‐GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), but there are limited real‐world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high‐grade B cell lymphoma treated with R‐GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy ( n = 100), those utilizing R‐GemOx as a bridge to ASCT or CAR T ( n = 83), and those aged 70 and older ( n = 71). Overall response rates (ORRs) for all patients treated with R‐GemOx were 45% with a complete response (CR) rate of 29%. The median event‐free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R‐GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R‐GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R‐GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R‐GemOx in the rapidly evolving landscape of R/R DLBCL therapies.

Background: Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is a commonly utilized chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), especially for patients ineligible for autologous stem cell transplant (ASCT) or chimeric antigen receptor T cell therapy (CAR T). R-GemOx is used as a comparator arm in several active phase III clinical trials for R/R DLBCL, including the POLARGO (polatuzumab vedotion and R-GemOx), STARGLO (glofitamab and GemOx), SUNMO (mosunetuzumab and polatuzumab vedotin), LOTIS-5 (loncastuximab tesirine and rituximab), and EPCORE DLBCL-1 (epcoritamab) studies. However, real-world data are limited to understand the patterns of use and outcomes of R-GemOx in the US. Methods: We developed a retrospective multicenter US cohort (known as LEO CReWE) of patients with R/R DLBCL and other aggressive B-cell lymphomas at the eight US academic centers participating in the LEO Cohort Study (NCT02736357). Patients first diagnosed with DLBCL (including transformed and high-grade B-cell lymphoma) from 2007 - 2022 who received second line (2L) or later therapy for R/R DLBCL with R-GemOx were included. Baseline characteristics, treatment, and follow-up data were abstracted by chart review. Index line of therapy was defined as the first receipt of R-GemOx therapy in the 2L or later setting. Intent for CAR T and/or ASCT was evaluated at each line of therapy based on medical records at the time of treatment initiation. Subgroup analyses were pre-planned in groups of special interest, including those treated with R-GemOx without intent for ASCT or CAR T, those treated as a bridge to CAR T, and those aged 70 and older. Results: 183 patients with R/R DLBCL treated with R-GemOx were included. At time of initiation of R-GemOx, median age was 68 years (range 21-88), with 71 patients (39%) aged 70+ and 18 (10%) aged 80+. Many patients had high risk features including 13% with high grade B-cell lymphoma and 56% with IPI 3 or greater. 21% had an ECOG performance status of 2 or greater. Patients received a median of 2 lines of therapy prior to the index line of R-GemOx (range 1-7). 52% of patients did not achieve a complete response (CR) to first-line therapy, and 20% relapsed <12 months from an initial CR. In all patients receiving R-GemOx, the overall response rate (ORR) was 45% (29% CR). At a median follow-up of 39 months, median EFS was 2.3 months (95% CI: 1.8-3.2), with 12-month EFS of 21% and a 24-month EFS of 15%. Median OS was 13.5 months (95% CI: 9.6-18.1), with a 12-month OS of 52% and a 24-month OS of 38%. In patients treated without intent for ASCT or CAR T, ORR was 33% (18% CR). Median EFS was 2.0 months (95% CI: 1.6-2.5) with 12- and 24-month EFS of 14% and 9%, respectively. Median OS was 9.5 months (95% CI: 6.6-16.1) with 12- and 24-month OS of 45% and 29%, respectively. In patients receiving R-GemOx as bridging to ASCT or CAR T, ORR was 57% (35% CR). 35% received CAR T and 14% received ASCT, while the remainder did not receive the intended therapy as part of this line. Median EFS was 3.6 months (95% CI: 1.8-5.2) with 12- and 24-month EFS of 28% and 25%, respectively. Median OS was 17.4 months (95% CI: 13.4-NR); 12- and 24-month OS were 61% and 50%, respectively. In patients aged 70+, ORR was 53% (33% CR). Median EFS was 2.3 months (95% CI: 1.6-5.2), with 12- and 24-month EFS of 20% and 18%, respectively. Median OS was 13.9 months (95% CI: 8.6-30.2); 12- and 24-month OS were 57% and 39%, respectively. Conclusion: This study represents the largest reported cohort of patients treated with R-GemOx in US academic centers to date. The ORR of 45% and CR rate of 29% CR, as well as median EFS and OS of 2.3 and 13.5 months, respectively, are consistent with findings from previous phase II studies; these results highlight that responses to R-GemOx are not durable and the vast majority of patients require additional therapy. This study demonstrates real-world evidence of the efficacy of R-GemOx in a large cohort of patients with R/R DLBCL from the US over a long period, including both transplant-eligible and -ineligible patients, and patients treated in the CAR T era. These data aid in providing a benchmark for active clinical trials in the rapidly evolving landscape of R/R DLBCL therapies and allow potential comparison to a real-world cohort of patients with a broad range of clinical characteristics.

Background: Mosunetuzumab (Mosun), a CD20xCD3 bispecific antibody, received accelerated approval for the intravenous treatment of patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ≥2 prior lines of systemic therapy. Mosun can be administered in the outpatient setting with a fixed treatment duration. In an ongoing Phase I/II study, Mosun administered subcutaneously (SC) induced durable responses with a manageable safety profile in pts with previously untreated low-tumor burden FL (LTB; Flinn et al. ASH 2023). Efficacy, safety and pharmacodynamic profiles of Mosun SC are being evaluated in an open-label, multicenter, Phase II study (MorningSun; NCT05207670) in pts with B-cell non-Hodgkin lymphomas, including previously untreated FL. Here we present >8-month follow-up efficacy, safety and biomarker data for Mosun SC in first-line, LTB FL. Methods: Pts had untreated Grade (Gr) 1 or 2 FL, LTB by Groupe d'Etude des Lymphomes Folliculaires criteria, Ann Arbor stage III/IV disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. Mosun SC injection was administered with step-up dosing in Cycle (C) 1 (Day [D] 1, 5mg; D8, 45mg; D15, 45mg), then 45mg on D1 of each 21-day cycle. Hospitalization was not mandatory. Pts with a complete metabolic response (CMR) after C8 could complete therapy. Pts with a partial metabolic response (PMR) or stable disease continued treatment for up to 17 cycles. Dexamethasone premedication was mandatory in C1 and C2 and optional thereafter. The primary endpoint was progression-free survival at 24 months. Exploratory analyses assessed cytokine levels in pts with versus without cytokine release syndrome (CRS) and pharmacodynamic changes in T and B cells in a subgroup of pts. Results: As of February 7, 2024, 65 pts were enrolled in US community (n=41) and academic (n=24) centers. At baseline, median age was 63 years (range: 34-82). Most pts had an ECOG PS of 0 (83.1%) or 1 (15.4%); 29 pts (44.6%) had extranodal involvement and 3 pts (4.6%) had B symptoms. Median duration of follow-up was 8.6 months (95% confidence interval [CI]: 5.7-10.9). Median number of cycles was 8 (range: 1-17). Among 60 pts with ≥1 post-baseline tumor assessment, the objective response rate was 95.0% (95% CI: 86.1-99.0; n=57) and CMR was 83.3% (95% CI: 71.5-91.7; n=50). Median time to response was 2.8 months (range: 2.3-8.3). At data cut-off, responses were ongoing in 48 pts with a CMR and in 5 pts with a PMR. In 64 safety-evaluable pts, the most common adverse event (AE) was injection-site reaction (70.3%; Gr 1, 65.6%; Gr 2, 4.7%). CRS by ASTCT occurred in 30 pts (46.9%; Gr 1, 39.1%; Gr 2, 7.8%); CRS events presented early in C1 (53.1%; Gr1, 45.3%; Gr2, 7.8%) and C2 (Gr1, 1.6%). Nineteen pts received CRS treatment (tocilizumab, 7.8%; steroids, 7.8%; tocilizumab + steroids, 4.7%; fluids, 3.1%; low-flow oxygen, 1.6%); 8 pts had a serious AE and were hospitalized. All CRS events resolved. Other common AEs included headache (45.3%; Gr 1, 29.7%; Gr 2, 15.6%), fatigue (45.3%; Gr 1, 35.9%; Gr 2, 9.4%), maculo-papular rash (31.3%; Gr 1, 14.1%; Gr 2, 15.6%; Gr 3, 1.6%), and increased alanine aminotransferase (28.1%; Gr 1, 21.9%; Gr 2, 4.7%; Gr 3, 1.6%). Gr 3/4 AEs in ≥5% of pts were neutropenia without fever (12.5%; Gr 3, 4.7%; Gr 4, 7.8%) and lymphopenia (7.8%; Gr 3, 1.6%; Gr 4, 6.3%). Suspected immune effector cell-associated neurotoxicity syndrome occurred in 2 pts (confusional state, Gr 1, n=1; Gr 2, n=1); all events resolved. Infections occurred in 30 pts (46.9%; Gr 1, 7.8%; Gr 2, 31.3%; Gr 3, 7.8%) with the most common (≥10%) being COVID-19 (17.2%; Gr 1, 7.8%; Gr 2, 7.8%; Gr 3, 1.6%) and upper respiratory tract infections (12.5%; Gr 1, 3.1%; Gr 2, 9.4%). One pt had a Gr 5 (fatal) AE 13.7 months after treatment was completed (reported as unrelated to Mosun; cause unknown). After the first Mosun dose, cytokine levels significantly increased on C1D2 (interleukin-6, n=44, p≤0.001; interferon-γ and tumor necrosis factor-α, n=41, p≤0.001). This spike in cytokine levels did not differ in pts with (n=19) versus without (n=25) CRS events in C1. Conclusions: Mosun SC monotherapy shows encouraging high efficacy as a fixed-duration treatment in first-line LTB FL. A manageable safety profile was reported, supporting ease of access for patients with drug administration in outpatient settings. Longer follow-up is needed to confirm long-term durability of response and safety.

e11051 Background: Limited data exist on patient (pt) experience and work productivity (WP) in MBC. VIRGO is a prospective OCS following >1200 pts with locally advanced or MBC receiving 1st-line hormonal therapy (HT) or chemotherapy (CT) in a real-world setting. We report baseline characteristics of 277 pts from the VIRGO PRO substudy and correlations between health-related quality of life (HRQoL), symptoms, activities of daily living, and WP. Methods: Symptom severity and interference (MD Anderson Symptom Inventory [MDASI]), functional status (Activity Level Scale [ALS] from the Rotterdam Symptom Checklist) and WP (Work Productivity and Activity Impairment Questionnaire) were assessed. Pts rated their HRQoL during the past week on a scale of 0–10. Results: See table. The five most severe symptoms at baseline were fatigue, decreased sexual interest, disturbed sleep, drowsiness, and emotional distress; these were reported with less severity in the HT cohort (24%-37% vs 42%-59%). Overall MDASI severity and interference correlated with WP measures in the CT (R = 0.46 to 0.78) and HT cohorts (0.36 to 0.94). Mean of the five most severe symptoms also significantly correlated with WP indices (R = 0.47 to 0.66). HRQoL correlated (p < 0.05) with all WP measures (R = -0.46 to -0.56) in the CT cohort and with % impairment while working (R = -0.65) and % overall work impairment (R = -0.71) in the HT cohort. In univariate regression analysis, MDASI symptom interference score was the best predictor of reduced WP (R2 = 0.52 while working; R2 = 0.48 for nonwork activities). Conclusions: MBC pts receiving CT and HT report significant work impairment. Results indicate moderate correlations between WP indices, HRQoL and symptom burden. [Table: see text]