P1187: SAFETY AND EFFICACY OF ANTICD20-CD3 BISPECIFIC T-CELL ENGAGING ANTIBODIES IN THE MANAGEMENT OF RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A SYSTEMATIC REVIEW OF CLINICAL TRIALS

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Relapsed/refractory diffuse large B-cell lymphoma (RRDLBCL) represents a major sub-group of non-Hodgkin lymphoma. Patients with RRDLBCL have poor clinical outcomes due to suboptimal therapeutic options. Several therapies are currently under development against RRDLBCL including bispecific antibodies (bsAbs). Aims: To analyze published evidence for the efficacy and safety of approved and unapproved antiCD20-CD3 T-cell engaging bsAbs for the treatment of RR-DLBCL. Methods: On January 29th, 2023, a systematic review of literature was conducted in PubMed, Embase, Web of Science and the ASH website using MeSH (medical subject heading) terms and keywords related to bispecific antibodies and non-Hodgkin lymphoma. The retrieved 2686 citations were screened by two reviewers for clinical trials published in English evaluating antiCD20-CD3 bsAbs against RRDLBCL. Results: We found 9 relevant clinical trials including 4 phase I/II, 3 phase I, 1 phase II, and 1 phase Ib/II. Total number of patients across the trials was 1272 with median age and prior number of therapies ranging from 19 to 91 and 1 to 14, respectively. In the trials, mosunetuzumab, glofitamab, epcoritamab, odronextamab, IGM-2323, and plamotamab were identified as antiCD20-CD3 bsAbs, which are evaluated against RRDLBCL as monotherapy and in combination regimens (Table). ORR/CR against the RRDLBCL was 35%/19.4% and 36%/20% for mosunetuzumab; 41.4%/28.8, -/40%, and 73%/51.5% for glofitamab; 56.5%/41.3%, 61.4%/38%, 92%/60%, and 84.6%/65.3% for epcoritamab; 36.6%/24.4% and 53%/37% for odronextamab; 35%/- against RRNHL (data immature for RRDLBCL) for IGM-2323; and 47.4%/26.3% for plamotamab. Patients with disease refractory to CAR-T cell therapy had an ORR of 46.2% and 33% for plamotamab and odronextamab, respectively (Table). Reported AEs were mostly hematological toxicities, cytokine release syndrome, immune effector-cell associated neurotoxicity syndrome and infections. Treatment discontinuation due to AEs was low across the trials and most of these were manageable. 4 deaths, none of which was related to drug and discontinuation of treatment due TRAEs by 34 patients, were reported in the trials. Summary/Conclusion: Based on our analysis, antiCD20-CD3 bsAbs are safe and efficacious. Among these drugs, glofitamab, epcoritamab and odronextamab as monotherapy and/or in combination regimens are the most effective therapies against RRDLBCL. - Drug (s) Author Efficacy ORR, CR per Lugano/RRC for ML criteria CRS Overall/G3 per ASTCT/ Lee et al criteria Overall Toxicity G≥3 per CTCAE CNS Toxicity G≥3 Per CTCAE Mosun IV Budde et al. aNHL 35% (n=45/129) and 19.4% (n=25), iNHL 66.2% (n=45/68) and 48.5% (33/68) 27.4%/1% 71.1% (n=197) 4.1% Mosun SC Budde et al. aNHL 36% (n=75), 20%; iNHL 82% (n=11), 64% 49% 27% None IV Glofit(dose-esc part) Hutchings et al. RRNHL 53.8% (92/171), 36.8% (63/171); RRDLBCL 41.4% (30/73), 28.8% (21/73) 50.3%, 3.5% 56.7% (97/171) 1.2% IV glofit dose-exp Dickinson et al. RRDLBCL CR 40% (44/110) 63%, 4% 62% 3% Glofit + Pola Hutchings et al. RRDLBCL 73% (24/33), 51.5% (17/33) 55%, none 52% (23/42) None SC epcore dose-esc part Hutchings et al. RRDLBCL 56.5% (26/46), 41.3% (19/46) 59%, none - None SC epcore dose-exp part Phillips et al. RRDLBCL, 61.4% (54/88), 38% (35/88) 49.7%, 2.5% 34.4% (54/157) 0.6% Epcore + GemOx Brody et al. RRDLBCL 92% (23/25), 60% (15/25) 70%, none 29.6% (8/27) 3.7% Epcore + R-DHAX/C Abrisqueta et al. RRDLBCL 84.6% (22/25), 65.3% (17/26); 41% NR None Odronextamab Bannerji et al. RRDLBCL 36.6% (30/82), 24.4% (20/82) 54%, 7% 82% (119/145) 3% Odronextamab KIM et al. RRDLBCL 53% (48/90), 37% (33/90) 53%, none NR None IGM-2323 Budde et al. RRNHL 35% (8/23) NR NR None Plamotamab Patel et al. RRDLBCL 47.4% (9/19), 26.3% (5/19) 72.2%, none 77.8% NR Keywords: Diffuse large cell lymphoma