[Column] CAR-T transformed treatment hopes for DLBCL, but Korea has a long way to go

According to the National Cancer Registry in 2024, there were 6,447 new cases of lymphoma in 2022, of which more than 90 percent were non-Hodgkin lymphoma. Among these, diffuse large B-cell lymphoma (DLBCL) is the most common subtype, with about 3,000 new cases diagnosed each year. Although DLBCL responds relatively well to first-line immunochemotherapy, 30-40 percent of all patients fail or become refractory to treatment. Only about half of these patients are candidates for autologous stem cell transplantation, and even then, about half face relapse after transplantation. 

Eventually, many patients progress to the third line of treatment and beyond, where the median survival is only about six months, with little hope of a cure. In the face of this hopelessness, a new treatment has emerged with a new name: CAR-T (chimeric antigen receptor T-cell therapy). 

CAR-T therapy is a personalized immune cell therapy that genetically reprograms a patient's immune cells, or T cells, to recognize and attack specific proteins (antigens) in cancer cells. T cells are extracted from the patient's blood and genetically engineered to express chimeric antigen receptors on the surface of the cells to recognize specific antigens on the surface of cancer cells, which are then grown outside the body and infused back into the patient. CAR-T cells, which combine different protein functions to perform new immune functions, are reminiscent of the Greek mythological complex creatures known as chimeras and are gaining attention as living therapies that weaponize the body's immune system to attack cancer cells. 

To date, seven CAR-T therapies have been approved by the U.S. FDA, three of which are indicated for DLBCL: Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel), and Breyanzi (lisocabtagene maraleucel). Kymriah and Yescarta were approved as third-line treatments in 2017 and Breyanzi in 2021, respectively. All three are effective in phase 2 clinical trials in DLBCL patients who have failed at least two prior therapies. 

In each study, about 40-50 percent of patients achieved complete remission, with 30-40 percent maintaining long-term survival and a potential cure. These are unheard-of outcomes in this previously untreatable population of patients with treatment-resistant DLBCL, which has been associated with extremely low survival rates and is considered to be a breakthrough that has virtually redrawn the survival curve. Based on this clinical evidence, CAR-T therapy is now the undisputed standard of care in the third-line setting.

Furthermore, CAR-T therapy has recently been validated as a second-line treatment for DLBCL patients who are refractory to first-line therapy or relapse early. The ZUMA-7 (Yescarta) and TRANSFORM (Breyanzi) clinical studies demonstrated superiority over autologous stem cell transplantation, and both have been expanded to second-line status in the U.S. and Europe starting in 2022. 

However, the situation in Korea is still limited. Currently, Kymriah is the only CAR-T treatment available in Korea, and it was approved by the Ministry of Food and Drug Safety in 2021. Since April 2022, it has been covered by health insurance for DLBCL patients in the third line and above. 

Still, the actual treatment environment and institutional foundation are lacking. CAR-T treatment can only be performed at institutions that are licensed to manage human cells under the Advanced Regenerative Biology Act or have met equivalent facilities and equipment standards. As of June 2025, three years after Kymriah became an insurance benefit, there were only 14 such institutions nationwide. This compares to nearly 50 hematopoietic stem cell transplant centers.

Even at authorized CAR-T centers, challenges remain in screening patients and determining treatment timing. Some patients clearly need CAR-T, but their condition doesn't align with reimbursement criteria, delaying or preventing treatment -- even when early intervention is clinically justified.

This gap between standards and reality creates challenges for clinicians and can lead to missed treatment opportunities for patients. Furthermore, with a CAR-T treatment costing around 400 million won ($294,200), access to reimbursement is a critical factor in treatment decisions. The current post-assessment-based reimbursement system can lead to financial burdens for healthcare organizations, including cuts in treatment fees, making them cautious in their treatment decisions. 

Because DLBCL is a rapidly progressive cancer, the timing of treatment is crucial to prognosis. With more than a month between the decision to treat with CAR-T and actual administration, access constraints, confusing insurance criteria, and delays in decision-making can lead to missed opportunities or suboptimal outcomes in this time-sensitive treatment. 

Meanwhile, bispecific antibodies (epcoritamab, glofitamab), which are considered the next generation of immunotherapies alongside CAR-T, have been approved in Korea, but are still not covered by insurance, limiting their availability to only a subset of patients. 

While DLBCL remains a difficult cancer to treat, the advent of innovative therapies, including CAR-T therapies, has opened the door for patients who have relapsed or have not responded to conventional treatments to be treated with the goal of a cure. However, for this hope to become a reality, the latest treatments must be applied at the clinically appropriate time, which requires infrastructure expansion, institutional improvement, and expanded access to treatment. Korea still faces the challenge of closing the gap with international standards of care in many aspects, from primary to tertiary care.