Epcoritamab Plus Lenalidomide Shows Promise in R/R DLBCL

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) face a challenging prognosis despite salvage chemotherapy and autologous stem cell transplantation. CAR T cell therapy, while providing long-term remission in only 40% of cases, underscores the need for alternative treatments. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, gained accelerated FDA approval for R/R DLBCL, showcasing promise for those not specified, including cases arising from indolent lymphoma and high-grade B-cell lymphoma post-≥2 lines of systemic therapy. Single-agent epcoritamab demonstrated notable responses (overall response rate(ORR), 63%; complete responses, 40%) and a manageable safety profile in the EPCORE NHL-1 trial.

Combining epcoritamab with diverse antineoplastic agents offers potential clinical benefits, prompting the investigation in EPCORE NHL-5. Irit Avivi Mazza and the team aimed to assess the safety, tolerability, and preliminary efficacy of epcoritamab and to define the recommended dose when coadministered with other antineoplastic agents in non-Hodgkin lymphoma patients. The focus of arm 1 was the evaluation of epcoritamab combined with lenalidomide in patients with R/R DLBCL. 

They performed an inclusive analysis in EPCORE NHL-5, a phase 1b/2, nonrandomized, open-label, multicenter study. In arm 1, adults with CD20+ R/R DLBCL (ECOG 0–2) received subcutaneous epcoritamab weekly during cycles 1–3 and every 4 weeks during cycles 4–12, along with oral lenalidomide once daily on days 1–21, spanning 12 cycles of 28 days each. Participants had received at least 1 prior systemic therapy combining anti-CD20 monoclonal antibody. The primary endpoint involved identifying dose-limiting toxicities (DLTs), while key secondary endpoints included assessing the best overall response (OR) and time to response by Lugano 2014 criteria. Safety endpoints focused on the severity and incidence of adverse events (AEs), encompassing AEs of special interest to epcoritamab, such as cytokine release syndrome (CRS), immune cell–associated neurotoxicity syndrome (ICANS), and clinical tumor lysis syndrome.

About 26 patients (median age: 71 years; DLBCL, n=24 [92%]; follicular lymphoma G3b, n=2 [8%]) received epcoritamab plus lenalidomide as of May 22, 2023. Median duration of epcoritamab exposure was 3.8 months (range, 0–7.5), and median duration of lenalidomide exposure was 4.0 months (range, 0.1–8.2); 15 patients (58%) remained on epcoritamab and lenalidomide. Median prior therapy lines were 1 (range: 1–4), with 15 patients (58%) having 1 prior line. 6 patients (23%) had previous CAR T therapy, and 2 pts underwent hematopoietic stem cell transplantation. 1 DLT (neutropenia) occurred. 

The most common G3–4 treatment-emergent AEs (TEAEs) were neutropenia (n=15; 58%), anemia (n=4; 15%), thrombocytopenia (n=4; 15%), and febrile neutropenia (n=3; 12%).  Primary granulocyte colony-stimulating factor prophylaxis was not mandatory. Epcoritamab discontinuation due to TEAEs occurred in 1 patient (3.8%; thrombocytopenia), and no TEAEs leading to epcoritamab-related deaths were reported. CRS was mostly low grade (73% [19/26] any grade; 65% G1–2; 8% G3) and occurred predominantly after the first full dose (C1D15). 

Preliminary biomarker analysis revealed consistent pharmacodynamic profiles, including predictable cytokine peaks and rapid, sustained depletion of peripheral B cells. 1 patient experienced G3 ICANS, resolving after 2 days. Among response-evaluable patients (n=24), the ORR was 75% (95% CI, 53.3, 90.2). Complete metabolic responses were seen in 14 patients (58%) and partial responses in 4 patients (17%), of which 3 were ongoing at the time of data cutoff. Median time to first response was 1.8 months (range, 1.0–2.8). Follow-up is ongoing.

The study concluded that the combination of epcoritamab and lenalidomide demonstrated promising antitumor activity and maintained a tolerable safety profile in patients with relapsed/refractory R/R DLBCL.

The study is sponsored by AbbVie

Source: https://ash.confex.com/ash/2023/webprogram/Paper180089.html

Clinical Trial: https://clinicaltrials.gov/study/NCT05283720

Mazza I A, Kim W S, Ko P S, et al. (2023). “Subcutaneous Epcoritamab Plus Lenalidomide in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma from EPCORE NHL-5. “Presented at ASH 2023 (Abstract 438).