Diffuse large B-cell lymphoma (DLBCL) is considered a difficult disease to treat due to its aggressive nature, but the emergence of new drugs has brought about a paradigm shift in its treatment.

As efforts for DLBCL progress towards a cure beyond extending survival, the role of bispecific antibody therapies is garnering attention.

Georg Lenz, Professor at Münster University Hospital in Germany, and Jung-ok Lee, Professor of Hematology and Oncology at Seoul National University Bundang Hospital, emphasized the diversified DLBCL treatment options and the importance of timely treatment for maximizing treatment efficacy during their interview with Daily Pharm.

Approximately 60% of DLBCL patients can expect a cure with first-line treatment, but around 30–40% of the remaining patients are resistant to first-line treatment or experience relapse.

Although no two patients are in the same situation, the two professors explained that achieving complete remission remains the primary goal, even for patients with relapsed or refractory (r/r) disease or those who have undergone third-line or later-line treatments.

Innovative new drugs such as “bispecific antibodies” and “antibody-drug conjugates (ADC)” are playing a major role in this process. However, DLBCL, which is characterized by rapid progression and aggressive characteristics among non-Hodgkin's lymphomas, is one disease that is difficult to cure.

Overseas, particularly in countries such as Germany, CAR-T therapy and bispecific antibody therapies have become clear treatment options depending on the recurrence period and health status of DLBCL patients.

According to Professor Georg, Germany uses various bispecific antibody therapies, including Epkinly, glofitamab, and odronextamab in the third-line treatment stage.

Professor Georg explained, “For r/r DLBCL patients receiving third-line treatment, bispecific antibody therapies become a treatment option. If CAR-T therapy was not administered in previous treatment stages, CAR-T therapy can also be considered as a treatment option in the third-line treatment stage.”

In contrast, in South Korea, the only CAR-T therapy available after second-line treatment is Kymriah, and bispecific antibody therapies are not reimbursed.

Regarding this, Professor Lee stated, “Polatuzumab vedotin in combination with R-CHP improved progression-free survival (PFS) compared to R-CHOP in the first-line treatment of DLBCL, and it is being used as a first-line treatment in several countries overseas. However, in Korea, R-CHOP remains the standard of care, so the rate of recurrence after first-line treatment will be relatively high.”

In particular, the difference in treatment access between Korea and other countries is evident after second-line treatment. This is because while three CAR-T therapies have been approved in the United States, only one, Kymriah, has been approved in Korea.

Professor Lee emphasized, “The domestic treatment environment falls short of global standards, and patients are missing out on real treatment opportunities. In addition to Kymriah, it is urgent to introduce additional CAR-T therapies such as Axi-cel and Liso-cel and apply reimbursement to bispecific antibodies such as Epkinly.”

With Epkinly prescriptions on the rise, the challenge is to overcome the remaining “treatment hurdles”

The reason why it is important for new drugs such as Epkinly, a bispecific antibody, to enter the regulatory system is because the ultimate goal of r/r DLBCL treatment is a complete cure.

Although bispecific antibodies lack long-term data compared to CAR-T therapies, which were developed earlier, they are considered to be a useful treatment option due to their relatively lower toxicity for elderly patients and others who cannot receive CAR-T therapy.

Professor Georg said, “I believe that approximately 3 years of long-term data accumulation will be sufficient. Considering the rapid changes in the treatment environment and the various data, I think there is a high possibility that Epkinly will firmly establish itself in the second-line treatment area in the near future.”

He added, “Based on the clinical data disclosed to date, the results of Epkinly combination therapy are showing positive trends. We optimistically anticipate that Epkinly may advance into an earlier line treatment option or even become a first-line treatment option used before the r/r stage, rather than completely replacing CAR-T therapy.”

According to three-year follow-up data presented at the American Society of Hematology (ASH) 2024 Annual Meeting, Epkinly achieved an overall response rate (ORR) of 59%, with 41% achieving complete remission.

Professor Lee explained, “It is encouraging that the 36-month survival rate of patients that reached complete remission was 63%. Additionally, the fact that the progression-free survival (PFS) curve showed a stable ‘plateau’ pattern after a certain point is a positive signal that the treatment effect may persist in the long term.”

Although direct comparison is difficult as long-term follow-up data has not yet been accumulated as much as for CAR-T therapy, Professor Lee believes that Epkinly is also expected to achieve high response rates, complete remission, and sustained response.

Clear differences exist in the global and domestic treatment environments… reimbursement needs to be realized

There are various conflicting opinions regarding the current position of CAR-T therapy and bispecific antibody therapy, including their complementary positions as a 'bridge therapy' before CAR-T therapy.

Both professors stated that it is difficult to determine the exact order considering reimbursement conditions and their clinical experience, but mentioned that Epkinly may be considered over CAR-T therapy in elderly patients in terms of adverse reaction management.

Professor Georg explained, “Epkinly has shown meaningful clinical efficacy in elderly or refractory patients who are difficult to treat with CAR-T therapy. In particular, it has a low and predictable incidence of cytokine release syndrome (CRS) and has been reported to be associated with minimal neurotoxicity in the form of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), making it highly safe.”

He added, “CAR-T therapy takes about a month to manufacture, so Epkinly may be considered first when time is limited. Although there are no age restrictions for either Epkinly or CAR-T, Epkinly may be a more appropriate choice for patients who are in poor overall health or are elderly.”

The problem remains that the reimbursement situation in Korea is still lacking in terms of a global standard of care.

He emphasized the need to improve the reimbursement system and access to treatment so that DLBCL patients in Korea can receive the latest global standard treatment.

Professor Lee said, “In South Korea, there is a gap between the global standard and Korea’s treatment in all lines of treatment, from the first to the third. Therefore, other effective CAR-T therapies besides Kymriah should be introduced as soon as possible, and bispecific antibody therapies, including Epkinly, should be included in the health insurance reimbursement system.”

Finally, he added, “As a hematologist treating DLBCL patients and a member of the Korean Society of Hematology, I hope that a medical environment is established where patients can receive bispecific antibody therapy as soon as possible. I feel a sense of responsibility as an expert and plan to actively voice my opinions and fulfill my role in both my academic society and as an individual physician.”