In patients with relapsed or refractory (R/R) follicular lymphoma (FL), the use of the subcutaneously administered bispecific antibody, epcoritamab plus rituximab + lenalidomide (R²) demonstrated a manageable safety profile with only low-grade cytokine release syndrome (CRS) events and a high complete metabolic response rate (CMR), according to data from a presentation at the recent American Society of Hematology Annual Meeting & Exposition.

Preliminary results from arm 2b of the phase 1/2 EPCORE NHL-2 trial (NCT04663347), which examined R² and epcoritamab in patients with R/R FL, demonstrated an overall response rate of 93% and a complete metabolic response rate of 61% at the first assessment.

At the ASH Meeting, Lorenzo Falchi MD, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY and colleagues presented updated data on a larger cohort and longer follow-up from arm 2b of EPCORE NHL-2.

In this study, adults with R/R CD20+ FL were treated with subcutaneous epcoritamab 48 mg + standard R² for 12 cycles of 28 days each. Epcoritamab was dosed as follows: every week, cycles 1 and 2; every 4 weeks, cycles ≥3 up to 2 years. During cycle 1 to lessen CRS, step-up epcoritamab dosing and corticosteroid prophylaxis were needed. PET-CT was employed to evaluate responses per Lugano 2014 criteria.

As of the data cutoff date of June 10, 2022, 62 patients had received epcoritamab (48 mg) + R². The average age was 65 years (range, 30–79), 58% of patients had stage IV disease, 52% had FLIPI 3–5, 31% had primary refractory disease, and 47% had experienced disease progression within 24 months after starting first-line treatment. Moreover, 50% had received 1 prior line of therapy (range, 1–9). Treatment was ongoing in 56 patients (90%), with an average follow-up of 4.0 months. A total of 6 patients discontinued therapy due to disease progression (n=4) or other reasons (death due to COVID-19, n=1; reason unknown, n=1).

The most common treatment-emergent AEs of any grade were CRS (37%; 27% grade 1, 10% grade 2, no grade 3–4), neutropenia (29%; 5% grade 1–2, 24% grade 3–4), fatigue (26%; 24% grade 1–2, 2% grade 3–4), and injection-site reactions (26%; all grade 1–2). The majority of CRS events (in 35% of all evaluable patients) occurred after the first full dose of epcoritamab. All CRS events resolved, no patients terminated treatment due to CRS, and 5 patients received tocilizumab. Immune effector cell- associated neurotoxicity syndrome [ICANS] (grade 1) transpired in 1 patient at 22 days from the beginning of treatment, and was resolved in 7 days. There were no clinical tumor lysis syndrome events.

Among 41 efficacy-evaluable patients, the overall response rate was 95% (39/41), with 73% of patients (30/41) achieving a complete metabolic response (CMR) as their best overall response. Most CMRs (27/30) were reached by the first assessment at week 6, and almost all (29/30) were ongoing at the time of data cutoff. Of the 9 patients with a partial metabolic response, 6 had an ongoing response at the time of data cutoff. The longest duration of response was 4.5+ months. Average progression-free survival was not achieved.

The authors concluded that among patients with R/R FL, subcutaneous epcoritamab + R2 demonstrated a manageable safety profile with only low-grade CRS events, primarily noted following the first full dose and all of which resolved and there were no new safety signals identified.

Dr. Falchi and colleagues stated, “ Data from this cohort are very encouraging with a high CMR rate observed in patients with R/R FL. These data are consistent with prior results from the EPCORE NHL-2 trial and supportive of ongoing investigation of epcoritamab + R² in patients with R/R FL. A phase 3 trial of epcoritamab + R² compared with R² alone in patients with R/R FL (EPCORE FL‑1) will open in 2022.” 

Source:

Falchi L. et al. Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update Presented at the 2022 American Society of Hematology Annual Meeting; December 10-13; New Orleans, LA. Abstract 609.