This article was originally appeared in onclive®.
Results from the phase 2 EPCORE DLBCL-3 trial (NCT05660967) showed that fixed-period subcutaneous administration of epcolitamab-bysp (Epkinley) induced reactions in newly diagnosed large B-cells not eligible to receive anthracyclines. Showed to be safe in elderly patients with lymphoma (LBCL). treatment based on. Data were presented at the 2024 ASH Annual Meeting.
In the complete analysis set (n = 45) and patients evaluable for response (n = 40), objective response rates (ORR) were 69% and 78%, and complete response (CR) rates were 62% and 78%, respectively. It was. 70%, and partial response (PR) rates were 7% and 8%. Of the 15 patients who responded and had evaluable minimal residual disease (MRD) status (including 14 who achieved CR and 1 who achieved PR), 93% of patients (n = 14/ 15) was MRD negative.
Median treatment duration was 6.6 months (range, 0.03-12.0), median number of treatment cycles was 7 (range, 1-12), and median patient time to response (TTR) was 1.5 months. (range, 1.2-12.0). 3.4). Furthermore, the data showed that the median time to CR was 2.5 months (range, 1.2-5.4). Responses deepened from PR to CR in seven patients, and eight of the nine who completed study treatment remained in CR at data cutoff.
Median follow-up for duration of response (DOR) was 6.4 months (range, 0.03+ to 14.1+) and median follow-up for duration of CR (DOCR) was 5.4 months (range, 0.03+ to 14.1+). . At 6 months, the chance of sustained response was 82% and CR was 84%. Additionally, 84% (n = 26/31) responses and 89% (n = 25/28) CR were maintained at data cutoff.
At 6 months, epcolitamab resulted in 73% progression-free survival (PFS) and 81% overall survival (OS). Neither PFS nor OS reached the median. Median follow-up was 8.1 months (range, 0.03+ to 17.0+) and 9.5 months (range, 0.4 to 17.7+). Data showed that 9 patients died due to disease progression (n = 6) or adverse effects (AEs; n = 3).
Frank Morschhauser, MD
“Epcolitamab monotherapy is a promising chemotherapy-free treatment option for elderly patients with comorbidities or newly diagnosed LBCL who are considered ineligible for anthracycline-based regimens”, CHU of the University of Lille said Frank Molschhauser, MD, professor of hematology at the Université de Lille. in Lille, France, he said in a presentation.
In an open-label phase 2 study, patients with newly diagnosed CD20-positive LBCL were randomly assigned 1:1 to receive epcolitab alone or in combination with lenalidomide (Revlimid). In the monotherapy group, patients received 48 mg of epcolitamab subcutaneously once weekly for cycles 1-3 and once every 4 weeks for cycles 4-12. Data cutoff date was September 21, 2024, and median follow-up was 9.5 months. (range, 0.4-17.7+).
The primary endpoint of this trial was CR rate based on Lugano criteria. Secondary endpoints include ORR, TTR, DOR, DOCR, PFS, OS, MRD negativity, and safety.
Patients with diffuse LBCL not otherwise specified (DLBCL), T cell- or histiocyte-rich DLBCL, double-hit or triple-hit DLBCL, or grade 3 follicular lymphoma with an immune effector cell encephalopathy score of at least 8 are eligible for enrollment. there was. Other requirements for study participation include having an ECOG performance status of 0-2, being over 80 years of age or having comorbidities over 75 years and therefore ineligible for anthracycline-containing treatment or cytotoxic chemotherapy. This includes diseases that can be measured by CT/MRI.
Researchers tested a total of 120 patients, and 88 were randomized. A total of 44 patients received epcolitamab monotherapy, 9 completed the treatment course, and 14 were still receiving treatment at the time of data cutoff.
Median patient age was 81 years (range, 77-95 years). Of note, 44% of patients were between 80 and 85 years of age, and 38% were 85 years of age or older. Additionally, 58% of patients had an International Prognostic Index score of 3 to 5. The most common cardiovascular comorbidities and risk factors included hypertension (78%), elevated cardiac enzymes (71%), atrial fibrillation (16%), and coronary artery disease. History of illness or myocardial infarction (16%). Other data showed that 87% of patients had cardiac and/or cardiovascular disorders and 40% had other comorbidities that made them poor candidates to receive cytotoxic therapy. Ta.
Cytokine release syndrome (CRS) occurred in 71% of patients, with grade 1 events occurring in 39%, grade 2 events in 27%, and grade 3 events in 5%. The median time to CRS onset after the first full dose was 15 hours (range, 9-26), and the median time to recovery was 2 days (range, 1-5). Researchers noted that 97% of CRS events were reported in cycle 1, with 32% of patients receiving tocilizumab (Actemra).
Immune effector cell-associated neurotoxicity syndrome (ICANS) affected 16% of patients, four of whom experienced concurrent CRS or capillary leak syndrome. Median time to ICANS onset was 28 days (range, 17-38), and all events resolved in a median of 2 days (range, 1-22). ICANS resulted in treatment delays in 11% of patients and treatment discontinuation in 2%.
Other toxicities include fatigue, constipation, nausea, and diarrhea. Serious infections occurred in 18% of patients, including 9% with severe COVID-19 infection. Neutropenia occurred in 9% of patients, and 18% discontinued treatment due to treatment-emergent AEs (TEAEs). Fatal TEAEs occurred in five patients, including COVID-19 (n = 2), cytomegalovirus reactivation (n = 1), tumor hemorrhage (n = 1), Lytic syndrome (n = 1) was included.
reference
Morschhauser F, Berrada D, Duell J, et al. First disclosure of EPCORE DLBCL-3: fixed-duration epcolitamab monotherapy for anthracycline-ineligible elderly (75 years and older) untreated patients with large B-cell lymphoma. blood. 2024;144(suppl 1):867. doi:10.1182/blood-2024-199271
