Epcoritamab/R-ICE Shows High Response in R/R DLBCL, Aids ASCT Eligibility
Multipotent stem cells in the bone marrow: © Juan Gärtner - stock.adobe.com
A novel combination therapy of epcoritamab (Epkinly) in conjunction with rituximab (Rituxan), ifosfamide, carboplatin, and etoposide (R-ICE) has demonstrated promising efficacy in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are candidates for autologous stem cell transplantation (ASCT).1
Data presented at the 30th European Hematology Association Congress revealed an overall response rate (ORR) of 87% and a complete response (CR) rate of 65%. These findings suggest that the integration of epcoritamab could significantly enhance the proportion of patients eligible for ASCT, a crucial component of curative intent in this challenging patient population.
“These results are particularly encouraging because many of the patients in this study had high-risk disease, having progressed rapidly after initial treatment,” said Raul Cordoba, MD, PhD, head of the Lymphoma Unit at the Fundacion Jimenez Diaz University Hospital, Madrid, Spain, in a press release. “This combination therapy of epcoritamab plus rituximab, ifosfamide, carboplatin, and etoposide offers a potential new treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma, providing high response rates and a bridge to potentially curative autologous stem cell transplantation."
The phase 1b/2 EPCORE NHL-2 trial (NCT04663347), specifically arm 10, evaluated this subcutaneous T-cell engaging bispecific antibody in 31 adult patients with R/R DLBCL. Beyond the high ORR and CR rates, the study reported a partial response rate of 23%. Notably, 65% of patients successfully proceeded to ASCT following the combination therapy. At 6 months posttreatment, an estimated 81% of responses were ongoing, 74% of patients remained progression-free, and 100% of patients were alive, indicating durable responses and favorable short-term outcomes.
The safety profile of the epcoritamab-R-ICE combination appears manageable. Cytokine release syndrome, a common adverse event with T-cell engaging therapies, occurred in 52% of patients but was exclusively low grade (grade 1/2) and resolved in all instances. No discontinuations due to treatment-emergent adverse events (TEAEs) were reported. The most frequent TEAEs observed were hematologic: neutropenia (74%), anemia (68%), and thrombocytopenia (68%). One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome, which also resolved. No clinical tumor lysis syndrome was observed, and while infections occurred in 58% of patients, only 16% were serious. Importantly, there were no grade 5 TEAEs, reinforcing the safety of this regimen in the context of R/R DLBCL.
Further analysis of the data underscored the broad applicability of the epcoritamab-R-ICE regimen across different patient subgroups. Among patients who progressed within 12 months after first-line treatment (n = 20), the ORR was 85% and the CR was 55%. For those who progressed after 12 months from first-line therapy, the ORR reached 91% and the CR was 82%.
Similarly, patients with 1 prior line of therapy demonstrated an 88% ORR and 68% CR, while those with more than 1 prior line of therapy achieved an 83% ORR and 50% CR. These data suggest consistent efficacy regardless of the timing of relapse or the number of prior treatment lines, which is crucial for a disease with diverse patient histories.
Genmab and AbbVie are collaboratively exploring epcoritamab across a range of hematologic malignancies and lines of therapy, with 5 ongoing phase 3 trials investigating its use as monotherapy and in combination.
Epcoritamab has received regulatory approval as monotherapy in certain lymphoma indications in the US, Japan, and the European Union. Most recently, in June 2024, it was approved for the treatment of R/R follicular lymphoma following 2 or more lines of therapy.2
