‘Bispecific antibody Epkinly shows miraculous results in 3rd-line treatment of DLBCL'

Medical professionals have expressed great expectations for Epkinly (epcoritamab), a third-line treatment for diffuse large B-cell lymphoma (DLBCL) recently introduced in Korea.

AbbVie Korea held a press conference last Wednesday to celebrate the approval of Epkinly. It is a bispecific antibody that targets CD20 and CD3 approved by the Ministry of Food and Drug Safety (MFDS) on June 20 for treating adult patients 18 and older with relapsed or refractory DLBCL after two or more systemic therapies.

Professor Yang Deok-hwan of the Department of Hematology at Chonnam National University Hwasun Hospital who heads the Lymphoma Research Committee of the Korean Society of Hematology (KSH) gave a presentation on "The latest treatment perspectives and unmet needs of DLBCL." Professor Kim Jin-seok of the Department of Hematology at Severance Hospital who heads the Multiple Myeloma Research Committee of the KSH presented "Key clinical results and significance of Epkinly as a bispecific antibody therapy.”

"According to the National Cancer Registry statistics in 2021, lymphoma is the 11th most common cancer among all cancers and the most common cancer among blood cancers. In addition, the number of newly diagnosed lymphoma patients reached 6,082 in 2021 and is continuously increasing," Professor Yang said. "There are about 100 lymphoma subtypes of which DLBCL is the most common and aggressive subtype, accounting for the largest share of lymphomas.

Yang explained that even after R-CHOP therapy, the standard of care for first-line DLBCL, 30-40 percent of patients relapse or become refractory to treatment and need to move on to the next line of treatment. Patients who relapse after receiving an autologous stem cell transplant as a second-line treatment have a poor prognosis, and patients who relapse after receiving CAR-T as a third-line treatment also have a poor outcome, he added.

"In other words, patients who relapse after receiving an autologous stem cell transplant in the second line have a poor prognosis, with overall lower response rates and worse survival. Currently, there are limited options in the third and subsequent lines of treatment, and there is no consistent standardized regimen, leaving a large unmet need and an urgent need for new options," Yang noted.

Professor Kim said, "Epcoritamab is a bispecific antibody that targets CD20 and CD3, with one arm attacking cancer cells and the other arm attracting the body's immune cells to the vicinity of the cancer cells to kill them,"

"The EPCORE NHL-1 study, which evaluated the efficacy and safety of Epkinly, showed an overall response rate (ORR) of 62 percent and a CR rate of 39 percent, comparable to CAR-T therapy," Professor Kim said. "In patients who achieved less than 10 percent complete remission with conventional therapy, this is a miraculous achievement, and the median overall survival (mOS) of 19.4 months at 20 months of follow-up is encouraging."

In the Q&A session that followed, participants asked about the characteristics and clinical roles of the CAR-T drug Kymriah (tisagenlecleucel) of Novartis, which is already covered as a third-line treatment in Korea, the bispecific antibody Columvi (glofitamab) of Roche introduced in Korea at the end of last year, and Epkinly.

Professors Yang and Kim explained that bispecific antibody therapies, including epcoritamab, have the advantage of being administered quickly and conveniently while showing similar effects to the existing CAR-T therapy Kymriah. They also emphasized the need to assess accurately a patient's response to treatment through microscopic residual disease (MRD) testing and to make the right choice based on the characteristics of each drug and the patient's situation.

"Kymriah is a CAR-T cell therapy using the patient's T cells, which attaches antibodies that attack cancer cells to the T cells to make them recognize and attack cancer cells. It is effective but manufacturing and administering the cells takes a long time and is very expensive. It can also have serious side effects," Professor Kim said.

Kim added that Columvi is also a bispecific antibody that targets CD20 and CD3 and works similarly to epcoritamab. However, it differs in how it is dosed and the predictability of side effects. Glofitamab is given intravenously, while epcoritamab is injected subcutaneously. Younger patients may prefer subcutaneous because of the shorter dosing time, and older patients may say, “I don't want to be poked in the stomach, I'll just take it intravenously.” However, doctors will look at the data and decide, and the follow-up period for both agents is still short.

“Columvi is given for a fixed number of cycles, whereas epcoritamab is given continuously until the disease progresses. From an economic point of view, 12 cycles (of glofitamab) is better,” Kim said. “However, from a patient's point of view, it's more psychologically reassuring to keep taking it until the disease progresses, because, with current technology, you don't know if there is any residual cancer left."

Professor Yang also said, "Glofitamab is given at regular intervals, whereas epcoritamab is started at a lower dose and gradually escalated, and side effects are more predictable, making it easier to manage," adding that Kymriah may not be suitable for older patients or those who need rapid treatment.