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

Epcoritamab (Epkinly) has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for patients with B-cell lymphomas.¹

This addition is for the treatment of patients as third line and subsequent therapy for patients with diffuse large B-cell lymphoma (DLBCL) with disease progression after transplant or chimeric antigen receptor (CAR) T-cell therapy, and as a preferred regimen for patients with histologic transformation of indolent lymphomas to DLBCL and no intention to proceed to transplant. This includes for the treatment of patients with disease progression after transplant or CAR T-cell therapy.

The NCCN provided a uniform consensus that the intervention is appropriate, leading to its addition in these guidelines.

“It is very important to have this drug added to the NCCN Guidelines as R/R DLBCL is a very difficult to treat patient population. Even with the addition of CAR T, we will have up to 60% of those patients either fail therapy or relapse. As well, a large number of patients will not be able to access CAR T. Given that, it is important to have a treatment that can be given after failure of CAR T or in situations where CAR T is not an option that has a high overall response rate and impressive but still maturing duration of response,” Tycel Phillips, MD, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, told Targeted Oncology^TM.

Epcoritamab is a T-cell engaging bispecific antibody was recently granted approval by the FDA for the treatment of adult patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after at least 2 lines of systemic therapy.²

This approval was supported by data from the LBCL cohort of the open-label, multi-center phase 2 pivotal EPCORE NHL-1 (NCT03625037) which showed that treatment with subcutaneous epcoritamab led to deep and durable responses among patients. This cohort of the EPCORE NHL-1 trial included 148 patients with R/R LBCL who were heavily pretreated and had an ECOG performance status of 0-2 with detectable disease on PET scan.

Additional data from the study showed that the primary end point of confirmed overall response rate (ORR) was met in the LBCL cohort at 61%, with 38% of those responses being a complete response. Additionally, the median duration of response in this cohort was 15.6 months.

"The safety profile indicated that the most common adverse event was cytokine release syndrome [CRS], which was noted in 51% of patients. Ninety-two percent of these events happened during cycle 1. It was most apparent at the first full dose. Most of these events were grade 1 [39%], which is important given that grade 1 CRS doesn’t require tocilizumab [Actemra] or hospitalization," added Phillips. "Additionally, only 10 of the 157 patients were noted to have ICANS. Again, similar to CRS most of these were low-grade. The ability to be able to predict when CRS is most likely to occur will be helpful for doctors, most commonly those who have not had any prior experience with bispecific antibodies. These results are quite impressive."

Epcoritamab continues to be evaluated as a monotherapy and in combination across lines of therapy for the treatment of patients with a range of hematologic malignancies. Some of these trials include an ongoing phase 3, open-label, randomized study evaluating epcoritamab alone in patients with R/R DLBCL (NCT04628494), an ongoing phase 3, open-label, randomized trial of epcoritamab in combination with rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for adult patients with newly diagnosed DLBCL (NCT05578976), and a phase 3, open-label trial assessing epcoritamab in combination with rituximab and lenalidomide (Revlimid) for patients with R/R follicular lymphoma.

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

"Treatment at current is to progression or intolerance. It will be important as time goes on to determine if there are some patients treated with epcoritamab that can have treatment stopped prior to those events. Also, the language recommends a 24 hour hospitalization on C1D15, which could limit the accessibility of the drugs initially. How sites without any associated hospital deal with this will be important. Another key to these drugs having the biggest impact in our patients is overcoming what I anticipate being the initial slow usage in non-academic sites. Once community sites get comfortable with drugs, which is likely to occur once they have established guidelines and a management strategy for CRS/ICANS, I believe bispecifics will be utilized as frequently as monoclonal antibodies are currently," concluded Phillips.

REFERENCES:

1. 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://tinyurl.com/unss2763

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 June 23, 2023. https://news.abbvie.com/article_display.cfm?article_id=12584