671 | Glofitamab for the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma, a Real‐world Evidence Study From the Cubic Consortium

Introduction: DLBCL treatment has been reshaped by cell-based therapies including chimeric antigen receptor T-cell (CAR T) therapy. However, outcomes for R/R DLBCL, especially after CAR T, remain dismal. Bispecific antibodies (BsAbs) have shown promising efficacy in this setting. Glofitamab, a 2:1 CD20:CD3 BsAb has been granted accelerated approval in the United States (US) by the FDA for R/R DLBCL based on a pivotal phase 2 study demonstrating an overall response rate (ORR) of 52% and complete response (CR) rate of 39% among heavily treated patients (pts). Despite the promising experience reported from clinical trials, real-world evidence remains limited. Here we present safety and efficacy of glofitamab in pts with DLBCL treated outside of a clinical trial in a large multicenter consortium. Methods: We conducted a retrospective review of adult pts with DLBCL treated with glofitamab outside of a clinical trial from 6 centers participating in the Collaborative US Bispecifics Consortium (CUBIC) between June 1, 2023 and February 1, 2025. Response was assessed per Lugano 2014 criteria. CRS and ICANS were graded by ASTCT criteria. Progression free survival (PFS) and overall survival (OS) were calculated from date of first BsAb dose and estimated using the Kaplan-Meier method. Results: A total of 69 pts with DLBCL were included in the analysis, including 22 pts (32%) with transformed follicular lymphoma (tFL). The median age was 68 (range 24–88) years with 62% male (n = 43); 28% (n = 19) of pts had ECOG ≥ 2 and thus would not have been candidates for the pivotal phase 2 study. The median number of prior lines of therapy was 3 (range 1–10), including 49% (n = 34) with prior CAR T exposure and 2 pts with prior autologous stem cell transplant. Rates of immune-related toxicity were consistent with clinical trial data with CRS occurring in 46% (n = 31) and ICANS occurring in 14% (n = 10). Toxicity grading was available for 41 pts at the time of abstract submission with grade 1 (G1) 24%, G2 15% and ICANS G1 5%, G2 2% and G3 2%. Among all pts, ORR was 52% with CR 32%. Pts exposed to prior CAR T had ORR 50% and CR 35%. Pts with disease refractory to the last therapy had ORR 45% and CR 26%. With a median follow up of 5.6 months among survivors (range, 1.1–18.7), the 6-month PFS was 41% (95% CI: 29%–53%), 12-month PFS was 33% (20%–46%), and median PFS was 3.7 months (95% CI: 2.1–8.1). Six-months OS was 69% (56%–79%), 12-month OS was 62% (46%–74%), and median OS was not reached. Conclusions: We present the largest RWE dataset of glofitamab for DLBCL with promising response rates and manageable toxicity. Our results are similar to those in the landmark trial leading to its accelerated approval, despite the significant proportion of pts with functional status that would have precluded their enrollment. Longer follow up and further study will help elucidate predictors of response, relapse and toxicity. Keywords: cellular therapies; aggressive B-cell non-Hodgkin lymphoma; immunotherapy Potential sources of conflict of interest: G. Shouse Consultant or advisory role: BeiGene, Kite Pharma, ADC Therapeutics S. Ahmed Consultant or advisory role: ADC therapeutics, KITE/Gilead, Genmab and BMS. Other remuneration: Research support to institution for clinical trials from Nektar, Merck, Xencor, Chimagen and Genmab, KITE/Gilead, Janssen, Caribou G. Salles Consultant or advisory role: Abbvie, Beigene, BMS, Ellipses, Foresight, Genentech/Roche, Genmab, Janssen, Incyte, Ipsen Kite/Gilead, Lilly, Merck, Novartis, Pfizer, SERB pharmaceuticals. Other remuneration: received research support from Abbvie, Genentech, Genmab Janssen, Ipsen, which was managed by his institution A. M. Bock Consultant or advisory role: Abbvie Other remuneration: Research funding (to institution): Genmab/Abbvie, Regeneron; Speakers Bureau: Genmab/Abbvie Y. Sawalha Consultant or advisory role: ADC, Genmab, and Genentech. Other remuneration: Research funding from BeiGene, Genmab, and AbbVie. S. Thiruvengadam Consultant or advisory role: Ipsen, Abbvie, Kite Other remuneration: Research Funding- GNE, ADC-T, Ipsen, Genmab/Abbvie C. R. Flowers Consultant or advisory role: Pharmacyclics/Janssen, Gilead, Adaptimmune, BeiGene, Seagen, Bayer, Spectrum, Celgene, Foresight Diagnostics, Denovo Biopharma, Sanofi, N-power medicine, Genmab, Genentech/Roche, Abbvie, Bio Ascend, BMS, AstraZeneca Stock ownership: Current holder of stock options in a privately-held company Foresight Diagnostics; 4D Other remuneration: Research Funding: Cellectis, Pfizer, Adaptimmune, Morphosys, Burroughs Wellcome Fund, Janssen Pharmaceuticals, TG Therapeutics, Xencor, Takeda, Eastern Cooperative Oncology Group, Iovance, Novartis, Acert, Foresight, Nektar, Kite, Ziopharm National Cancer Institute, Allogene, Karyopharm, Sanofi, Amgen, BostonGene, Genmab, Genentech/Roche, Cancer Prevention and Research Institute of TExas: CPRIT Scholar in Cancer Research, EMD Serono, Abbvie N. Epperla Consultant or advisory role: Lilly, Novartis, Ipsen Other remuneration: Speakers bureau: Genentech, BeiGene A. Herrera Consultant or advisory role: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Abbvie, Allogene Therapeutics Other remuneration: Research funding: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca A. V. Danilov Consultant or advisory role: Abbvie, ADCT, AstraZeneca, BeiGene, Bristol-Meyers-Squibb, GenMab, Janssen, Lilly Oncology, MEI Pharma, Merck, Nurix, Regeneron and Roche Other remuneration: Research funding from Abbvie, AstraZeneca, Beigene, GenMab, Lilly Oncology, Merck, Nurix and Regeneron L. Falchi Consultant or advisory role: Consultancy: Roche, Genentech, Genmab, AbbVie, Sanofi, Evolveimmune, AstraZeneca, Merck Advisory board: AbbVie, Genentech, ADC therapeutics, Seagen, Ipsen, Johnson & Johnson Honoraria: Roche, Genmab, AbbVie, Kite Educational grants: Genmab, AbbVie, Roche, Kite Other remuneration: Research funding: Roche, Genentech, Genmab, AbbVie, Innate Pharma, Beigene AstraZeneca