Dr Falchi on the Safety of Fixed-Duration Epcoritamab Plus Lenalidomide/Rituximab in R/R Follicular Lymphoma

"From a safety point of view, we didn't record any new safety signals. Cytopenia, particularly neutropenia, remains the dominant adverse [effect]."

Lorenzo Falchi, MD, an assistant attending physician at Memorial Sloan Kettering Cancer Center, discussed the safety and pharmacodynamic profile of fixed-duration epcoritamab-bysp (Epkinly) in combination with lenalidomide (Revlimid) and rituximab (Rituxan) in patients with relapsed/refractory follicular lymphoma, based on findings from arm 2 of the phase 1/2 EPCORE NHL-2 trial (NCT04663347).

This arm of the study evaluated the triplet regimen in a cohort of patients with relapsed/refractory follicular lymphoma following prior therapy. With a median follow-up exceeding 2 years, the combination demonstrated a manageable safety profile without the emergence of new safety signals. The most frequently observed adverse effects (AEs) were hematologic, with neutropenia being the most prominent cytopenia. This toxicity was attributed to both lenalidomide and, to a lesser extent, epcoritamab.

Cytokine release syndrome (CRS), a known class AE of T cell–engaging therapies, was reported in 52% of patients. However, the vast majority of events were low grade: most were grade 1 or 2, and only 2% of patients experienced grade 3 CRS. No grade 4 or 5 CRS was reported. Injection site reactions were also observed but did not result in treatment discontinuation. The remaining AE profile was consistent with known toxicities of lenalidomide and rituximab.

In addition to safety, pharmacodynamic correlates were assessed. The combination regimen produced rapid, profound, and sustained B-cell depletion, similar to the effect of epcoritamab monotherapy. Notably, T-cell and natural killer cell subpopulations increased during treatment, particularly through cycles 4 to 6, indicating effective immune activation and engagement throughout the dosing period.

Falchi noted that although COVID-19 infection rates were high during the trial due to the timing of enrollment, this did not confound interpretation of regimen-related safety signals. Overall, the combination of epcoritamab, lenalidomide, and rituximab in a fixed-duration schedule appeared to maintain the immunologic activity of epcoritamab monotherapy with a safety profile aligned with known toxicities of the individual agents.