Cases Show How Epcoritamab Revived CAR T Cells After Relapse in DLBCL

CD19-directed chimeric antigen receptor (CAR) T-cell therapy can offer sustained remission for patients with diffuse large B-cell lymphoma (DLBCL). But up to 60% of patients eventually relapse, leaving few treatment options.

When relapse occurs, a key question is whether to try a cytotoxic therapy, such as chemotherapy, or to pursue a T-cell engaging therapy, such as the bispecific epcoritamab. A recent report on 6 patients treated this way appeared in eJHaem, the open access journal of the British Hematology Society, suggesting this sequencing is not only effective, but may help revive CART T cells in the body and lead to remission.¹

bispecific antibody | Image: Genmab, AbbVie

Epcoritamab (Epkinly; Genmab, AbbVie) is a bispecific T-cell engager directed at CD3 x CD20; others are Genentech’s glofitamab (Columvi) and mosunetuzumab (Lunsumio), which the authors say have each shown some ability to boost CAR copy numbers if given after CAR T relapse. The data reported in eJHaem are the first such results for epcoritamab, they write.

Blood samples taken before and after CAR T treatment were collected from 6 patients; 4 were treated with tisagenlecleucel (tisa-cel/Kymriah; Novartis) and 2 were treated with axicabtagene ciloleucel (axi-cel/Yescarta; KitePharma). Polymerase chain reaction testing evaluated genomic DNA for CAR copies, and other tests evaluated cell damage and exhaustion. Of note, 4 patients received epcoritamab within 30 days of relapse, with 1 patient treated on day 8.

The study authors, from Juntendo University School of Medicine, Tokyo, Japan, highlighted results for 2 patients treated at their own insitution. The first was a 76-male who initially achieved complete metabolic remission (CMR) after 6 rounds of rituximab and chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone, or R-CHOP). He relapsed after 12 months and received a different rituximab combination (with gemcitabine, dexamethasone, and cisplatin, or R-GDP). After a second relapse 14 months later, tisa-cel brought remission. A third relapse occurred after 16 months, and epcoritamab followed. CAR copy numbers recovered quickly, the authors wrote.

“The patient has completed 10 cycles and continues epcoritamab therapy while maintaining CMR. CAR copy numbers were retained above levels observed before relapse,” they wrote.

The second patient highlighted is a 64-year-old female whose lymphoma was described as “primary cutaneous DLBCL, leg type.” She also had 6 rounds of R-CHOP and relapsed 3 months later; a second relapse came after 1 cycle of R-GDP.

The patient received axi-cel as third-line therapy. After 2 months, scans showed CMR, but a rash appeared on her leg and a biopsy confirmed relapse. Following epcoritamab, her CAR copies increased, and authors said the patient had received 12 courses of epcoritamab.

“Administration of cytotoxic anticancer agents post-CAR-T therapy generally reduces CAR-T cells,” the authors wrote. “In contrast, our observations implicate that epcoritamab enhances circulating CAR-T cell numbers and viability in peripheral blood.” The authors say the results may aid decision making for patients with DLBCL who experience a relapse following CAR T.

Reference

Yanashima K, Furukawa Y, Ishii M, et al. Early epcoritamab administration revives CAR-T cells in relapsed/refractory B-cell lymphomas. eJHaem, 2025;6:e70079. doi:10.1002/jha2.70079