P1154: EFFICACY OF SUBCUTANEOUS EPCORITAMAB VS AXI-CEL IN R/R DLBCL CAR T-NAIVE AND CAR T-ELIGIBLE PATIENTS: AN INDIRECT COMPARISON

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Epcoritamab, an off-the-shelf, subcutaneous CD3xCD20 T-cell–engaging bispecific antibody that redirects T cells to eliminate malignant CD20+ B cells, showed single-agent efficacy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) with a manageable safety profile. The phase 1/2 EPCORE NHL-1 trial (NCT03625037) of epcoritamab in patients with R/R DLBCL who received ≥2 prior lines of systemic therapy demonstrated high complete response (CR) and minimal residual disease rates. To contextualize the data with that of other T-cell engagers, indirect comparisons are warranted. Aims: We conducted an unanchored, matching-adjusted indirect comparison of the efficacy of epcoritamab with that of axicabtagene ciloleucel (axi-cel) in patients with R/R DLBCL. Two groups from the EPCORE NHL-1 trial were analyzed: all CAR T-naive patients and CAR T-naive patients considered eligible for CAR T therapy. Methods: Published data on overall response rate (ORR), CR rate, and overall survival (OS) for axi-cel (ZUMA-1 trial, N=101) and individual patient-level data (IPD) for epcoritamab (EPCORE NHL-1 trial) were used to conduct the comparisons. Patients enrolled in EPCORE NHL-1 who had prior CAR T therapy were excluded because ZUMA-1 included only patients without prior CAR T therapy. Analyses were adjusted for imbalances in baseline characteristics between IPD from EPCORE NHL-1 and aggregate data from ZUMA-1. Propensity score weights resulting from the adjustment were applied to estimate risk differences for ORR and CR rate, and weighted Cox proportional-hazards models were used to estimate OS hazard ratio (HR). Subgroup analyses of CAR T-eligible patients were conducted to assess patients with more similar clinical characteristics. Results: Compared with the ZUMA-1 population, respectively, the majority of patients enrolled in the EPCORE NHL-1 trial (N=86) had no prior CAR T exposure, were men (61.6% vs 23.8%) with a median age of 69.5 y (vs 58.0 y), and were refractory to ≥2 consecutive lines of therapy (62.8% vs 53.5%). Among the CAR T-adjusted matched population, response rates were not statistically different in those treated with epcoritamab vs axi-cel (ORR: 73.4% vs 74.3%, respectively; difference in ORR: −0.8%; P=0.927; CR rate: 48.5% vs 54.5%; difference in CR rate, −6.0%; P=0.583). In a subgroup of CAR T-naive patients that were CAR T eligible and treated with epcoritamab (N=50), response rates also did not significantly differ from those in patients treated with axi-cel (ORR 72.7% vs 74.3%, respectively; difference in ORR: −1.6%; P=0.873; CR rate: 47.7% vs 54.5%; difference in CR rate, −6.8%; P=0.576). In all CAR T-naive patients, OS was not statistically different between those treated with epcoritamab vs axi-cel (HR: 0.695; 95% CI: 0.351, 1.376; P=0.297). Similarly, the CAR T-eligible subpopulation treated with epcoritamab did not have statistically different OS vs axi-cel (HR: 0.708; 95% CI: 0.309, 1.626; P=0.416). Summary/Conclusion: Findings from this cross-study comparison suggest that epcoritamab is a promising, emerging, novel therapy with no statistically significant difference in efficacy vs axi-cel in patients with highly refractory, hard-to-treat DLBCL. These findings must be interpreted with caution as there is a higher level of uncertainty with indirect treatment comparison vs randomized controlled trials. Additional analyses with longer follow-up are needed to better understand the therapeutic potential of epcoritamab as an off-the shelf, subcutaneously delivered core therapy for these patients. Keywords: Clinical trial, Non-Hodgkin’s lymphoma, DLBCL