When used as a first-line therapy, subcutaneous bispecific antibody epcoritamab combined with rituximab plus lenalidomide (R²) demonstrated promising efficacy, based on high response rates, and a manageable safety profile with no new safety signals, according to data presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition.

Lorenzo Falchi MD, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY and colleagues presented initial data from arm 6 of EPCORE NHL-2, exploring the safety and efficacy of epcoritamab + R² as a first-line therapy in patients with follicular lymphoma (FL). The research indicates that the combination of epcoritamab with rituximab + lenalidomide (R²) may result in greater and more durable responses compared to R² alone.

The study involved adults with previously untreated CD20+ FL grade 1 to 3A who met Groupe d’Etude des Lymphomes Folliculaires [GELF] criteria for treatment who received subcutaneous epcoritamab 48 mg + R² for 12 cycles of 28 days each. Epcoritamab was administered every week in cycles 1 to 2 and every 4 weeks subsequently, for up to 2 years of treatment. During cycle 1, step-up epcoritamab dosing and corticosteroid prophylaxis were required to mitigate the incidence of cytokine release syndrome [CRS]. Response to treatment was assessed by PET-CT, per Lugano criteria.

As of the data cutoff date of June 10, 2022, 41 treatment-naive patients with FL had received epcoritamab + R². The average age was 57 years and average time from initial diagnosis to first dose of epcoritamab was 12 weeks.

The majority (85%) had grade 2 or 3A FL; 39% and 51% had stage 3 and 4 disease, respectively. With a median follow-up of 4.4 months (range, 0.7–7.5), treatment was ongoing in 36 (88%) patients; 5 (12%) discontinued treatment, 3 due to adverse events (AEs) and 2 due to disease progression. All patients experienced a treatment-emergent AE (TEAE), with 36 (88%) having events that were regarded as related to epcoritamab. The most common TEAEs were: cytokine release syndrome [CRS]: (51%; 34% grade 1, 17% grade 2, no grade 3 to 4), neutropenia (41%; 17% grade 1 to 2, 24% grade 3 to 4), pyrexia (41%; all grade 1 to 2), injection-site reactions (37%; all grade 1 to 2), fatigue (29%; all grade 1 to 2), headache (29%; 27% grade 1 to 2, 2% grade 3 to 4), constipation (27%; all grade 1 to 2), and rash (27%; 20% grade 1 to 2, 7% grade 3 to 4).

The majority of CRS events (in 41% of all patients) occurred after the first full dose of epcoritamab, all resolved (average time to resolution, 4 days; tocilizumab administered in 5 patients), and none led to treatment discontinuation. Immune effector cell-associated neurotoxicity syndrome (ICANS) and clinical tumor lysis syndrome were not observed. 1 fatal TEAE was observed (COVID-19 pneumonia, believed not related to epcoritamab).

Among efficacy-evaluable patients (n=29), the overall response rate was 90% (26/29), with 69% (20/29) having a complete metabolic response (CMR) as their best overall response. At the time of data cutoff, all CMRs and partial metabolic responses were ongoing.

The researchers indicated that subcutaneous epcoritamab + R² showed a manageable safety profile, related to that observed in the R/R setting, with no new safety signals, no ICANS events, and only low-grade CRS events, all of which resolved.

Dr. Falchi and colleagues concluded, “This regimen showed encouraging efficacy, based on high response rates, when used as a first-line treatment for FL. These data support further clinical evaluation of epcoritamab + R² in previously untreated patients with FL.”

Source:

Falchi L, Abrisqueta P, Nijland M, et al. Subcutaneous Epcoritamab in Combination with Rituximab + Lenalidomide (R²) for First-Line Treatment of Follicular Lymphoma: Initial Results from Phase 1/2 Trial Presented at the 2022 American Society of Hematology Annual Meeting; December 10-13; New Orleans, LA. Abstract 611.