FDA Approves Epcoritamab for Relapsed/Refractory DLBCL


The FDA has approved the first T-cell–engaging bispecific antibody, epcoritamab-bysp (Epkinly), for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma, after 2 or more lines of systemic therapies.



The FDA has approved the first T-cell–engaging bispecific antibody, epcoritamab-bysp (Epkinly), for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBCL), after 2 or more lines of systemic therapies.1,2

It is recommended that epcoritamab be administered using step-up dosing in cycle 1, which comprises 0.16 mg on day 1, 0.8 mg on day 8, and 48 mg on days 15 and 22. This should be followed by a fixed weekly dose of 48 mg during cycles 2 to 3, an every-other-week dose for cycle 4 to 9, and then every-four-weeks on the first day of subsequent cycles.

The accelerated approval is supported by findings from the phase 1/2 EPCORE NHL-1 trial (NCT03625037), in which epcoritamab elicited an overall response rate (ORR) of 61% (95% CI, 53%-69%), which included a complete response (CR) rate of 38% in patients with CD20-positive DLBCL who were enrolled to the expansion cohort of the trial (n = 148). At a median follow-up of 9.8 months in responders, the median duration of response (DOR) with the agent was estimated to be 15.6 months (95% CI, 9.7-not reached [NR]).

"Patients with DLBCL who relapse or are refractory to currently available therapies have limited options. Generally, the prognosis for these patients is poor and management of this aggressive disease can be challenging," said Tycel Philips, MD, associate professor in the Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, at City of Hope, stated in a press release. "Epcoritamab is a subcutaneous bispecific antibody that offers an additional treatment option for this patient population. With this approval, patients who are in need of additional therapy may have the opportunity to receive epcoritamab after failure to respond or relapse after two or more systemic therapies."

Patients with relapsed or refractory, CD20-positive mature B-cell neoplasms who received at least 2 previous lines of therapy, including at least 1 anti-CD20 monoclonal antibody, were enrolled to the trial. They were required to have an ECOG performance status of 0 to 2, and were allowed to have received previous CAR T-cell therapy

Study participants received 48 mg of subcutaneous epcoritamab once weekly during cycles 1 to 3, then twice weekly in cycles 4 to 9, and 4 times weekly thereafter. Treatment continued until disease progression or intolerable toxicity.

ORR per independent review committee served as the trial’s primary end point. Key secondary end points included DOR, CR rate, time to response (TTR), overall survival (OS), progression-free survival (PFS), and safety/tolerability.

Of the 148 patients who comprised the expansion cohort, 86% had DLBCL NOS. Specifically, 27% had DLBCL transformed from indolent lymphoma and 14% had HGBCL. The median number of prior lines of treatment received in this group was 3, with a range of 2 to 11 lines. Notably, 30% of patients received 2 prior therapies, 30% received 3 prior therapies, and 40% received at least 4 prior therapies.

In terms of prior treatment, 18% of patients previously underwent autologous hematopoietic stem cell transplantation. Thirty-nine percent of patients had prior exposure to CAR T-cell therapy and 29% were refractory to the modality. The majority of patients (82%) were refractory to the last treatment that they received.

Data presented at the 2022 EHA Congress showed that 157 patients with LBCL, the ORR with epcoritamab was 63% (95% CI, 55%-71%), which included a CR rate of 39% (95% CI, 31%-47%).3 Three patients had stable disease and 24% experienced progressive disease.

The median DOR in those who achieved a CR was not yet reached (NR), and the median time to CR was 2.7 months (range, 1.2-11.1). At a median follow-up of 10.7 months (range, 0.3-17.9), the overall median DOR was 12.0 months (range, 0+ to 15.5+), and the median TTR was 1.4 months (range, 1.0-8.4).

At this time point, the median OS with the bispecific antibody was NR. The OS r ates at 6 and 12 months were 70.6% (95% CI, 62.7%-77.2%) and 56.9% (95% CI, 47.3%-65.4%), respectively. Moreover, the median PFS in those who achieved a CR was also NR. The majority of complete responders (89%) remained in CR at 9 months. The overall median PFS was 4.4 months (95% CI, 2.0-7.9); the PFS rate at 6 months was 43.9% (95% CI, 35.7%-51.7%).

Regarding safety, the most common toxicities reported in at least 20% of patients who received the bispecific antibody included cytokine release syndrome (CRS), fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea.1,2 The most frequently experienced lab abnormalities that were grade 3 to 4 in severity and reported in 10% or more of patients comprised decreased lymphocyte count, neutrophil count, white blood cell count, hemoglobin, and platelet count.

The prescribing information for epcoritamab has a Boxed Warning for serious or life-threatening CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). Of the 157 patients with relapsed or refractory LBCL who received the agent at the recommended dose, 51% experienced CRS and 6% had ICANS; 15% of patients had serious infections.1 Of those who experienced CRS with the agent, this effect was grade 1, 2, and 3, in 37%, 17%, and 2.5% of patients, repectively. In those who had ICANS, 4.5% had a grade 1 event, 1.3% had a grade 2 event, and 0.6% had a grade 5 event.

"The FDA approval of [epcoritamab] represents a new treatment mechanism of action for third line patients [with] DLBCL. As a non-chemotherapy, single-agent treatment for [this population], we hope that [epcoritamab] can effectively treat this aggressive cancer type and can be used for patient care quickly and in an off the shelf form for physicians," Thomas Hudson, MD, senior vice president of research and development and chief scientific officer of AbbVie, added in the press release. "The approval is just the first step, with our partner Genmab, toward a shared goal of developing a core therapy for patients with B-cell malignances."


  1. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA. May 19, 2023. Accessed May 19, 2023.
  2. EPKINLY™ (epcoritamab-bysp) approved by US FDA as the first and only bispecific antibody to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). News release. AbbVie. May 19, 2023. Accessed May 19, 2023.
  3. Thieblemont C, Phillips T, Ghesquieres H, et al. Primary results of subcutaneous epcoritamab dose expansion in patients with relapsed or refractory large B-cell lymphoma: a phase 2 study. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract LB2364
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