EHA2024 Hybrid Congress

Background:
Epcoritamab (epcor) is a novel, subcutaneous (SC) CD3xCD20 bispecific antibody (bsAb) providing deep and durable responses and manageable safety in relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2systemic therapies, based on the EPCORE NHL-1 trial (NCT03625037). Intravenous (IV) mosunetuzumab (mosun) and IV odronextamab (odro) are CD20xCD3 bsAbs with efficacy and safety in the same indication based on the GO29781 (NCT02500407) and ELM-2 (NCT03888105) trials, respectively. No direct comparisons of efficacy and safety of bsAbs have been made.

Aims:
To conduct matching-adjusted indirect comparisons (MAICs) of the efficacy and safety of epcor vs mosun orodro in patients (pts) with R/R FL after ≥2 systemic therapies.

Methods:
Efficacy comparisons used individual pt data from EPCORE NHL-1 (04/2023 data cutoff [DCO]; median follow-up [MFU]: 17 months [mo]) and aggregate pt data from GO29781 (DCO: 05/2023; MFU: 37 mo) and ELM-2(DCO: 08/2023; MFU: 18 mo). The epcor vs mosun comparison used pts represented in both trials. All epcor pts were compared with odro pts. Safety comparisons used individual pt data from the EPCORE NHL-1 FL cycle 1optimization (OPT) cohort with 3-step up dosing, dexamethasone, and hydration (DCO: 01/2024; MFU: 5.7mo). Treatment cohorts were match-adjusted and balanced on key baseline characteristics. Comparisons included overall response rates (ORR), complete responses (CR), progression-free survival (PFS), overall survival (OS), incidence of grade (G)≥2 cytokine release syndrome (CRS), and immune effector cell–associated neurotoxicity syndrome (ICANS). Propensity score weights were used to estimate odds ratios (OR)for responses and adverse events, and weighted Cox proportional-hazards models were used to estimate hazard ratios (HR) for survival.

Results:
Compared with mosun pts (N=90), epcor pts (N=81) before adjustment were older (age ≥60 years: 57% vs50%), had more advanced disease (stage III/IV; 85% vs 77%), were more double-refractory (70% vs 53%), had more prior R2 (19% vs 9%), and had less prior ASCT (20% vs 31%). Compared with odro pts (N=128), epcor pts(N=128) were older (age ≥65 years: 52% vs 37%), were more double-refractory (70% vs 41%), had more prior LOTs (≥3: 63% vs 55%), had more prior R2 (21% vs 13%), and had less prior ASCT (19% vs 30%). After match-adjustment, epcor provided numerically higher response rates than mosun: ORR: 91% vs 80%, P=0.07; CR: 73%vs 60%; P=0.16. Adjusted comparisons accounting for the impact of COVID-19 showed no statistically significant difference in PFS and OS for epcor vs mosun. After match-adjustment, epcor provided significantly higher ORR (91% vs 80%, P=0.02) and comparable CR rates (67% vs 73%, P=0.38) vs odro. There was no statistically significant difference in PFS and OS for epcor vs odro. CRS G≥2 was lower for epcor vs mosun(10.8% vs 18.9%, P=0.44). No ICANS was observed with epcor vs 4.4% with mosun (P<0.001). Similarly, there were fewer CRS G≥2 events for epcor vs odro (14.7% vs 18.3%, P=0.64) and no ICANS for epcor vs 0.8% for odro (Table).

Summary/Conclusion:
This match-adjusted cross-study analysis suggests that, as well as being a convenient subcutaneous option, treatment with epcoritamab had a trend toward higher response rates and improved safety for CRS grade ≥2and ICANS compared with mosunetuzumab or odronextamab. Notwithstanding the limitations of the study, these findings underscore the benefits of epcoritamab in R/R FL.

Table. Matching-adjusted indirect comparison for safety.
Epcoritamab vs Mosunetuzumab Epcoritamab vs Odronextamab CRS G≥210.8% vs 18.9%OR: 0.52 (95% CI: 0.10, 2.74), P=0.4414.7% vs 18.3%OR: 0.77 (95% CI: 0.25, 2.39), P=0.64ICANS0% vs 4.4%OR: 0 (95% CI: 0, 0), P<0.0010% vs 0.8%OR: 0 (95% CI: 0, 0), P<0.001