Epcoritamab Plus Lenalidomide Reduces Progression Risk in R/R DLBCL; Other Lenalidomide Regimens Show Benefit

Positive topline results from the phase 3 EPCORE DLBCL-4 trial showed that epcoritamab plus lenalidomide significantly reduced the risk of disease progression or death by 60% compared with R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The open-label trial included 379 adult patients with R/R DLBCL who had previously received at least one line of systemic antineoplastic therapy including anti-CD20 monoclonal antibody-containing combination chemotherapy, and who had failed or were not candidates for autologous stem cell transplantation and were ineligible for or unable to receive CAR-T therapy.

Patients were randomly assigned to receive subcutaneous epcoritamab and oral lenalidomide for twelve 28-day cycles, or intravenously infused rituximab plus gemcitabine plus oxaliplatin (R-GemOx) for up to four cycles. On the primary endpoint of progression-free survival, the combination reduced the risk of progression or death by 60% under US censoring rules (hazard ratio [HR], 0.40 [95% CI, 0.30-0.55]; P <.0001) and by 56% under non-US censoring rules (HR, 0.44 [95% CI, 0.33-0.60]; P <.0001). The safety profile was consistent with the known profiles of each agent. AbbVie and Genmab plan to consult with regulatory authorities to discuss the path forward, and full results will be presented at a future medical meeting.

In a separate long-term analysis of the phase III AUGMENT trial, lenalidomide plus rituximab (R2) continued to show benefit over rituximab plus placebo in patients with relapsed or refractory indolent non-Hodgkin lymphoma. At a median follow-up of 65.9 months among 358 intent-to-treat patients, the hazard ratio for progression-free survival was 0.50 (95% CI = 0.38–0.66) and for overall survival was 0.59 (95% CI = 0.37–0.95). In the 295 patients with follicular lymphoma, the PFS HR was 0.43 (95% CI = 0.32–0.59); among the 66 patients aged 70 years or older, the PFS HR was 0.62 (95% CI = 0.33–1.17). The investigators concluded that improved long-term efficacy and manageable safety were observed with R2, and that the data continue to support R2 as a standard of care for relapsed or refractory indolent non-Hodgkin lymphoma. These findings were published in the Journal of Clinical Oncology.

A phase 2 multi-center trial evaluated penpulimab, lenalidomide, and R-GemOx in 54 patients with relapsed or refractory DLBCL. Among 38 patients treated without intent for autologous stem cell transplantation (ASCT) consolidation, the overall response rate was 63.2% and the complete response rate was 52.6%, with a median progression-free survival of 21.2 months and median overall survival not reached. In 16 patients who received the regimen as a bridge to ASCT, the ORR was 75.0% and the CRR was 68.8%, and neither PFS nor OS was reached. The most frequent adverse events were neutropenia (36/54, 66.6%), anemia (32/54, 59.2%), and thrombocytopenia (15/54, 27.7%). There were 14 deaths, one due to COVID-19 infection and 13 due to disease progression; no deaths were considered treatment-related. The study appeared in BMC Medicine.