The recent developments in Large B-cell lymphoma (LBCL) management have introduced a new subcutaneous treatment, epcoritamab-bysp (Epkinly), targeting the elderly population with limited options for entry into anthracycline-based regimens. The phase 2 EPCORE DLBCL-3 study presented at the American Society of Hematology Annual Meeting-2024 shows how this therapy is effective and safe for this susceptible patient population by providing a chemotherapy-free regimen. A total of 45 patients were enrolled in the study, of whom 40 were evaluable for response.
The overall response rate based on the objective response rate (ORR) was 78% with a complete response rate (CR) of 70% and a partial response rate (PR) of 8%. Negative minimal residual disease (MRD) was established in the 15 patients, with the median time to the response being 1.5 months and to CR 2.5 months. The responses grew more profound, and later, several PRs progressed into CRs. At the time of data collection in the study, 8 out of 9 patients who completed treatment maintained sustained CRs.
Overall, the median follow-up for the duration of response (DOR) and duration of complete response (DOCR) was 6.4 and 5.4 months respectively. The overall response rate at 6-months was 82%, with 84% of those in CR sustaining this status. At 6 months, the progression-free survival rate was 73%, while the overall survival rate was 81%, with median progression-free survival and overall survival (PFS-OS) not yet reached.
It included a trial group of patients aged between 77-95 years (mean = 81 years) with comorbid disease that contraindicated cytotoxic chemotherapy. Concerning age, 44% of the patients belonged to the group of 80-85 years and 38% of patients were more than 85 years old. The majority of the patients had cardiovascular comorbidities including hypertension in 78%, raised cardiac enzyme level in 71%, new-onset atrial fibrillation in 16%, and prior history of coronary artery disease (CAD) or previous myocardial infarction (MI) in 16% of patients. Other comorbidities accounted for 40% which excluded them from anthracycline-based regimens.
In the open-label phase 2 trial, newly diagnosed CD20-positive LBCL patients were randomly assigned in a 1:1 ratio to receive either epcoritamab alone or epcoritamab plus lenalidomide (Revlimid). In the monotherapy, epcoritamab was given subcutaneously 48 mg once weekly from cycles 1-3, and then every 4 weeks from cycles 4-12. The data cutoff date for the trial was September 21, 2024. With a median follow-up duration of 9.5 months (range, 0.4-17.7+ months).
Despite the effectiveness of the therapy, it carried relatively significant side effects. In all the patients, 71% of them experienced cytokine release syndrome (CRS) where most of them had been rated to be either mild or moderate. Therefore, it can also be stated that CRS appeared no later than 15 hours post-dosing, and all the symptoms had resolved by 48 hours median. The immune-effector cell-associated neurotoxicity syndrome (ICANS) has been reported in 16% of the patients and the median time to onset was 28 days and all events resolved within a median time of 2 days.
Other adverse events reported in the current studies were fatigue, constipation, nausea, and diarrhea. Clinically significant infection occurred in 18% including coronavirus disease 2019 (COVID-19) in 9%. Of the subjects, 18% had treatment-emergent adverse events (TEAEs) that resulted in treatment discontinuation, while 5 out of the patients developed fatal TEAEs due to (COVID-19), cytomegalovirus reactivation, and tumor lysis syndrome.
Epcoritamab monotherapy provides a new, chemotherapy-free option for older patients with LBCL who are not eligible candidates for standard therapy because of age and comorbidities. The results of this trial highlight its ability to provide deep and durable responses with acceptable risks of adverse effects, especially in an age group with few remaining therapeutic options. “This is going to redefine the treatment for LBCL in older adults,” predicted Franck Morschhauser, MD, PhD, University of Lille, France.
This study represents a significant step toward expanding treatment accessibility for elderly LBCL patients, with ongoing research needed to confirm long-term benefits and refine safety protocols.
Reference: Morschhauser F, Belada D, Duell J, et al. EPCORE DLBCL-3 first disclosure: fixed-duration epcoritamab monotherapy in older (≥75 y), anthracycline-ineligible patients with previously untreated large b-cell lymphoma. Blood. 2024;144(suppl 1):867. doi:10.1182/blood-2024-199271
