NCCN Adds Epcoritamab to Clinical Practice Guidelines in Oncology for B-Cell Lymphomas

Epcoritamab-bysp (Epkinly) has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for B-cell Lymphomas in the third- or later-line setting for the treatment of patients with diffuse large B-cell lymphoma (DLBCL), including patients with disease progression after transplant or CAR T-cell therapy, and as a category 2A preferred regimen for patients with histologic transformation of indolent lymphoma to DLBCL with no intention to proceed to transplant, including patients with disease progression after transplant or CAR T-cell therapy.¹

The recommendation is based on consensus from the NCCN that the agent is appropriate. The announcement comes just one month after the FDA granted accelerated approval to the agent for the treatment of patients with relapsed/refractory DLBCL not otherwise specified (DLBCL-NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after 2 or more lines of therapy.²

“The NCCN Guidelines are a resource for treating various types of cancer and providing healthcare providers with information for making informed treatment decisions,” Judith Klimovsky, MD, executive vice president and chief development officer of Genmab, said in a press release. “We are pleased that the NCCN has updated its Guidelines to include epcoritamab in a speedy manner.”

Epcoritamab received FDA approval based on response rate and durability of response data from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).1,2 Efficacy was evaluated in 148 patients with relapsed/refractory DLBCL-NOS, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody–containing therapy.

The primary end point of the trial was overall response rate (ORR) assessed by an independent review committee per Lugano 2014 criteria. Results showed that epcoritamab led to an ORR of 61% (95% CI, 53%-69%), with 38% of patients achieving complete response. At a median follow-up of 9.8 months among responders, the estimated median duration of response (DOR) was 15.6 months (95% CI, 9.7–not reached).

Per the label, the regimen is to be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity. The recommended dose follows step-up dosing in cycle 1, at 0.16 mg on day 1, 0.8 mg on day 8, and 48 mg on day 15 and day 22, followed by fixed dosing of 48 mg weekly dosing during cycles 2 through 3, every other week during cycle 4 through 9, and then every four weeks on day 1 of subsequent cycles.

Notably, the prescribing information has a boxed warning for serious or life-threatening cytokine release syndrome (CRS), as well as life-threatening or fatal immune effector cell–associated neurotoxicity syndrome (ICANS). Among the 157 patients with relapsed/refractory large B-cell lymphoma who received epcoritamab at the recommended dose, CRS occurred in 51% of patients (grade 1, 37%; grade 2, 17%; grade 3, 2.5%), ICANS was reported in 6% (grade 1, 4.5%; grade 2, 1.3%; grade 5, 0.6%), and serious infections occurred in 15%.

Other common adverse effects were fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3/4 laboratory abnormalities were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Continued approval of the agent for this indication will depend on verification and description of clinical benefit in confirmatory trials, including but not limited to the following phase 3 trials: NCT04628494, NCT05578976, and NCT05409066.

References

• Genmab announces epcoritamab added to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for ‘B-cell lymphomas.’ News release. Genmab A/S. June 22, 2023. Accessed June 23, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-epcoritamab-added-national-comprehensive-cancer
• FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. News release. FDA. May 19, 2023. Accessed June 23, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell