Background: Outcomes are poor with standard palliative chemotherapy in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who fail or are ineligible for autologous stem cell transplant (ASCT). Rituximab with gemcitabine + oxaliplatin (GemOx) was associated with a complete response rate of 33% (Cazelles et al, Leuk Lymphoma 2021); new approaches are needed. Epcoritamab, a subcutaneously administered bispecific antibody, targets CD3 on T cells and CD20 on B cells. Epcoritamab had a manageable safety profile and antitumor activity in heavily pretreated B-cell non-Hodgkin lymphoma (NHL), including DLBCL, in the EPCORE NHL-1 dose-escalation trial. Epcoritamab + standard B-cell NHL therapies are being evaluated in the phase 1/2 EPCORE NHL-2 trial (NCT04663347); results from arm 5 are shown here.
Aims: To evaluate the safety and preliminary efficacy of epcoritamab + GemOx in pts with R/R DLBCL who are ineligible for ASCT.
Methods: Adults who had R/R CD20+ DLBCL and had failed or were ineligible for ASCT were enrolled. Pts received epcoritamab (weekly, cycle [C] 1–3; every 2 wk, C4–9; every 4 wk, C≥10) and GemOx (every 2 wk, C1–4) until disease progression or unacceptable toxicity (28 d/C). To mitigate CRS, step-up epcoritamab dosing and prophylactic corticosteroids were required in C1. Response was assessed by PET-CT according to Lugano 2014 criteria. Informed consent was obtained.
Results: As of the data cutoff date (December 1, 2021), 27 pts (median age, 71 y; range, 47–87) had received epcoritamab + GemOx (epcoritamab 24 mg, n=3; 48 mg, n=24). Most pts were stage IV (56%), primary refractory (56%), and/or refractory to last therapy (70%). Number of prior therapies ranged from 1–13, with a median of 2 prior therapies. Treatment was ongoing in 16 pts (59%), with a median follow-up of 6.0 mo (range, 1.0–11.1). Treatment-emergent AEs (any grade [G]) in >50% of pts were CRS (70%), thrombocytopenia (70%), neutropenia (56%), anemia (52%), and infections (52%). Most cases of CRS occurred in C1; all were G1/2 and resolved (median time to resolution, 2 d). No pts discontinued epcoritamab due to CRS. ICANS (G3) and tumor lysis syndrome (G3) were reported in 1 pt each. Six pts had G5 AEs; the contribution of epcoritamab could not be ruled out by the investigator in 2 pts: small bowel perforation in 72-year-old with transformed DLBCL and extensive gastrointestinal involvement (achieved complete metabolic response [CMR]); acute hepatitis/multiorgan failure in 68-year-old with transformed DLBCL and liver involvement (achieved CMR). Of the 4 pts who had fatal AEs unrelated to epcoritamab according to the investigator: 2 pts aged 87 y had primary refractory disease and 2 pts aged 74 y had multiple comorbidities. Antitumor response is shown in Table 1. All 3 pts previously treated with CAR T-cell therapy remained on study treatment and in response (2 CMR, 1 partial metabolic response).
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Summary/Conclusion: No unexpected safety findings were observed for epcoritamab + GemOx when considering the individual safety profiles of epcoritamab and GemOx. Given the high unmet need in this R/R pt population, these initial data are encouraging; further clinical evaluation is warranted.