Indirect Comparison of Epcoritamab Versus Axicabtagene Ciloleucel in Chimeric Antigen Receptor T-Cell-Eligible and -Naive Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

BACKGROUND

In the absence of a head-to-head trial of off-the-shelf subcutaneous epcoritamab, a novel CD3xCD20 bispecific antibody, versus chimeric antigen receptor T-cell therapy (CAR T), a matching-adjusted indirect comparison (MAIC) of epcoritamab versus axicabtagene ciloleucel (axi-cel) efficacy was conducted in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) with ≥ 2 prior lines of systemic therapy.

METHODS

The MAIC used epcoritamab patient-level data from EPCORE NHL-1 (NCT03625037; April 2023 data cutoff) and axi-cel aggregated data from ZUMA-1 (NCT02348216). Patients without prior CAR T were matched to the ZUMA-1 population; weighted regression models were used to estimate absolute differences in overall response rate (ORR) and complete response (CR) rate, and weighted Cox proportional-hazards models were used to estimate hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS).

RESULTS

EPCORE NHL-1 included patients without prior CAR T (N = 86, 61.9%) and a CAR T-eligible subset (N = 50, 36.0%) selected via ZUMA-1 inclusion/exclusion criteria. Comparing epcoritamab versus axi-cel, ORR was 73.5% versus 74.3%, respectively (adjusted absolute differences [95% CI]: -0.7% (-18.3, 16.8; P = .933) and CR rate was 48.7% versus 54.5%, respectively (adjusted absolute difference [95% CI] -5.7% [-27.1, 15.7]; P = .599). There was no statistically significant difference in PFS (adjusted HR [95% CI]: 1.009 [0.572-1.778]; P = .975) or OS (adjusted HR [95% CI]: 0.826 [0.444-1.536]; P = .546). Similar results were observed in the CAR T-eligible cohort.

CONCLUSION

This MAIC found comparative efficacy between axi-cel and subcutaneous epcoritamab, addressing a critical unmet need for therapeutic alternatives to CAR T for patients with third-line or later relapsed/refractory DLBCL.