CELL INTELLIGENCE · 肿瘤细胞治疗研究

Epcoritamab is a CD3 CD20 T-cell-engaging bispecific antibody approved for the treatment of various types of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) and R/R follicular lymphoma (FL), after at least two lines of systemic therapy.

Here, we develop and calibrate repeated time-to-event models to assess the impact of optimized step-up dosing (SUD) regimens and the effect of intravenous fluids and/or corticosteroids on cytokine release syndrome (CRS) risk. The analysis used pooled data from 600 patients with aggressive non-Hodgkin lymphoma (aNHL) and indolent NHL (iNHL) who received subcutaneous epcoritamab in 28-day cycles in the EPCORE NHL-1 and EPCORE NHL-3 studies (NCT03625037, NCT04542824).

In the calibrated model, prior CAR T cell therapy (125/600 patients [20. 8%]) was associated with a 69. 7% reduction (95% confidence interval [CI], 38. 2-85. 2) in the maximum stimulatory effect of epcoritamab on the hazard of Grade 2 CRS. Intravenous fluids or dexamethasone during Cycle (C)1 were associated with a 2. 89-fold (95% CI, 1. 57-5. 30) increase in the half-maximal effective plasma concentration of epcoritamab on stimulation (S50).

Furthermore, prophylaxis with intravenous fluids and dexamethasone during C1 was associated with a 3. 79-fold (95% CI, 1. 65-8. 73) increase in S50. Simulations show that the use of dexamethasone further reduces Grade 2 CRS risk compared with prednisone in patients with aNHL/iNHL.

Moreover, a 3-SUD design further reduces CRS risk in patients with iNHL.

Overall, our models showed that the approved 2-SUD regimen for R/R LBCL and 3-SUD regimen for R/R FL-together with intravenous fluids and dexamethasone prophylaxis-are adequate to reduce Grade 2 CRS risk.