Relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) continues to present significant treatment challenges, particularly for patients who are eligible for autologous stem cell transplant (ASCT) but fail initial salvage regimens. Epkinly (epcoritamab), developed by Genmab and Abbvie, is a subcutaneously delivered CD3×CD20 bispecific T-cell engager (BiTE) that secured FDA accelerated approval in 2023 for r/r DLBCL in patients who received at least two prior lines of systemic therapy. In 2024, the label was further expanded to include relapsed follicular lymphoma. Epkinly is showing compelling results across a range of combination trials.
Arm 10 of the Phase Ib/II EPCORE NHL-2 trial expands Epkinly’s clinical utility by combining it with the chemoimmunotherapy regimen R-ICE, which includes rituximab, ifosfamide, carboplatin and etoposide. Data presented at the European Hematology Association (EHA) 2025 Hybrid Congress, held on 12-15 June, demonstrated that the combination of Epkinly and R-ICE produced an overall response rate of 87% and a complete response rate of 65% in transplant-eligible patients with r/r DLBCL. Following treatment, 65% of patients proceeded to ASCT, suggesting the combination may serve effectively as a bridging strategy. The safety profile was manageable, featuring low-grade cytokine release syndrome (CRS) and predictable treatment-emergent adverse events (TEAEs). CRS occurred in 52% of patients, though all cases were grade 1 or 2. The most frequently observed TEAEs were haematologic in nature, including neutropenia (74%), thrombocytopenia (68%) and anaemia (68%), indicating careful monitoring during treatment. These rates align with expectations for R-ICE. One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome, which resolved.
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Dr Raul Cordoba emphasised that the regimen has the potential to induce deep and early responses. He noted that it may eventually change the role of ASCT, either by improving the likelihood of patients reaching transplant or by delaying or eliminating the need for it. Should longer-term progression-free survival be sustained, Epkinly + R-ICE will emerge as a new standard in the salvage setting.
Epkinly’s subcutaneous administration offers a significant logistical advantage over IV-administered bispecifics and CAR-T therapies. Its short administration time supports use in outpatient settings, which could facilitate broader adoption. However, one challenge is its indefinite treatment duration as Epkinly is continued until disease progression or unacceptable toxicity. This differs from fixed duration treatment regimens used with Epkinly’s bispecific counterparts and CAR-T therapies, which may influence physician preference.
Despite this, Epkinly remains well-positioned among bispecific competitors. While Roche’s bispecifics Lunsumio (mosunetuzumab) and Columvi (glofitamab) have both advanced in DLBCL, with Columvi approved for DLBCL not otherwise specified following at least two prior lines of therapy. However, Columvi has demonstrated grade 3 CRS events, which may raise safety considerations in certain patient populations. Regeneron Pharmaceuticals’ Ordspono (odronextamab) is also progressing in late-stage development for DLBCL. In contrast, Epkinly benefits from a more favourable safety profile, particularly in terms of CRS severity, as well as a comprehensive and diverse clinical trial program. Phase III trials are ongoing in first-line DLBCL (Epkinly + R-CHOP), and in the relapsed setting, where it is being evaluated as monotherapy versus investigator-choice chemotherapy. In follicular lymphoma, trials are evaluating Epkinly in combination with Revlimid (lenalidomide) and rituximab in both first-line and relapsed patient populations. Additional programs are ongoing in chronic lymphocytic leukaemia, Richter’s transformation, pediatric B-cell malignancies, and evolving first-line opportunities.
According to GlobalData’s analyst consensus forecast, Epkinly is projected to reach annual sales of $3.94bn by 2031. This growth is expected to be driven by widespread label expansions and increasing adoption across lymphoma subtypes. Epkinly is well-positioned to become a standard of care across multiple B-cell malignancies due to its flexibility in treatment combinations, convenient subcutaneous administration, and maturing efficacy data.
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