‘Yescarta demonstrates potential for long-term survival’

Targets patients who relapsed within 12 months… expands role in second-line treatment

Changes the use of CAR-T timing… Changes in Korean treatment landscape gains attention

The role of CAR-T therapy is expanding in the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

With long-term survival data for Yescarta being secured in patients who relapse or become refractory within 12 months of first-line treatment, treatment strategies in the second-line setting are also beginning to evolve.

On June 24, Gilead Sciences Korea held a press conference in Seoul to mark the domestic launch of its CAR-T therapy ‘Yescarta (axicabtagene ciloleucel),’ highlighting the current treatment landscape and the therapy's clinical value in relapsed/refractory DLBCL.

Professor Dok Hyun Yoon of the Division of Oncology at Asan Medical Center emphasized that substantial unmet needs remain for patients with relapsed or refractory DLBCL.

Professor Dok Hyun Yoon of the Division of Oncology at Asan Medical Center

Professor Yoon said, “DLBCL is the most common subtype of non-Hodgkin lymphoma, and some patients experience relapse or become refractory even after first-line treatment. In particular, patients who relapse within one year have a very poor prognosis, making the choice of treatment in the second-line setting significantly important for long-term outcomes.”

DLBCL is one of the most aggressive forms of lymphoma. First-line treatment typically consists of R-CHOP-based chemoimmunotherapy (rituximab, cyclophosphamide, vincristine, and prednisone). While many patients can achieve complete remission with this regimen, approximately 30–40% eventually experience relapse or refractory disease.

The challenge arises after relapse. In Korea, salvage chemotherapy followed by autologous stem cell transplantation remains the primary treatment strategy. However, treatment outcomes remain limited in real-world practice.

“Response rates to salvage chemotherapy are generally low in relapsed or refractory patients, and only a limited number of patients proceed to autologous stem cell transplantation. Given the limitations of conventional therapies, it is important to implement advanced treatment options at the appropriate time to improve long-term survival.”

Value of second-line CAR-T therapy confirmed in clinical trials

Professor Seok Jin Kim, Division of Hematology-Oncology at Samsung Medical Center

Professor Seok Jin Kim, Division of Hematology-Oncology at Samsung Medical Center, reviewed results from the pivotal ZUMA-7 study and emphasized the importance of the timing of CAR-T therapy.

Yescarta is a CAR-T therapy manufactured using a patient’s own T cells, which are genetically engineered to recognize CD19 expressed on the surface of cancer cells.

In Korea, Yescarta is approved for second-line treatment of adult patients with DLBCL that relapses within 12 months after first-line chemoimmunotherapy or is refractory to treatment, and for the treatment of relapsed or refractory DLBCL and primary mediastinal B-cell lymphoma (PMBCL) after at least two prior lines of systemic therapy.

Notably, it is currently the only CAR-T therapy approved in Korea as a second-line treatment.

The Phase III ZUMA-7 study compared Yescarta with standard-of-care treatment, including salvage chemotherapy and stem cell transplantation, in patients with large B-cell lymphoma who relapsed within 12 months of first-line therapy or were refractory to treatment.

Results showed that Yescarta significantly improved event-free survival (EFS) compared with standard treatment and reduced the risk of relapse or death by 60%. In a four-year follow-up analysis, Yescarta reduced the risk of death by 27%, while the median overall survival (OS) had not yet been reached.

“Even though a substantial number of patients in the standard-care arm later received CAR-T therapy or bispecific antibody treatments, the survival benefit of Yescarta was maintained. This demonstrates the importance of using CAR-T therapy at the appropriate stage rather than repeatedly administering multiple lines of therapy after relapse.”

He added, “Patients who relapse within one year or are refractory from the outset face an extremely high risk of death from the disease. That is why CAR-T should be considered from the second-line setting.”

Kim further noted, “More than half of these patients survived beyond four years, even though long-term survival would have been difficult to expect in the past in this population. The treatment goal in relapsed/refractory DLBCL is evolving from simple disease control to achieving long-term survival.”

Gap remains between global standards and Korean clinical practice

Experts also highlighted the shift toward earlier use of CAR-T therapy.

The current National Comprehensive Cancer Network (NCCN) guidelines recommend CAR-T therapy as a major second-line treatment option for patients with DLBCL who relapse within 12 months of first-line therapy or are refractory to treatment.

In the past, patients with relapsed disease were first treated with salvage chemotherapy and autologous stem cell transplantation, with CAR-T therapy considered only later in the treatment sequence. However, treatment paradigms are increasingly shifting toward earlier use of CAR-T therapy in high-risk patients.

Professor Kim said, “CAR-T therapy has already become a standard second-line treatment option in many countries. Korea also needs to establish an environment that allows patients to receive this therapy at the appropriate time.”

Yescarta is currently reimbursed in 30 countries worldwide, and the cumulative number of treated patients has surpassed 28,700. Gilead Sciences Korea stated that it plans to continue discussions to broaden treatment access for patients in Korea.