Yescarta speeds up CAR-T therapy, providing a new option for relapsed lymphoma 바카라사이트 추천

[by Yu, Suin] "The advent of chimeric antigen receptor T-cell (CAR-T) therapy has marked a significant transformation in the therapeutic landscape with diffuse large B-cell lymphoma (DLBCL) in Korea. The availability of Yescarta (axicabtagene ciloleucel) for high-risk patients experiencing relapse within one year is expected to further accelerate this paradigm shift."

Professor Kim Seok-jin of the Department of Hematology and Oncology at Samsung Medical Center in Seoul recently underscored the clinical significance of 바카라사이트 추천's domestic approval and highlighted its potential to reshape the therapeutic landscape. Developed by Gilead Sciences in the United States, 바카라사이트 추천 is a CAR-T therapy that involves the ex vivo extraction of autologous T lymphocytes, their genetic modification to express receptors specific for CD19 (a B-cell surface antigen) and their subsequent reinfusion into the patient. Through this mechanism, the engineered T cells selectively recognize, target, and eliminate CD19-expressing malignant cells.

◇바카라사이트 추천 becomes the third CAR-T therapy approved in Korea after Kymriah and Carvykti, gaining indications for second- and third-line DLBCL treatment

Yescarta received approval from the U.S. Food and Drug Administration (FDA) in 2017 and from the European Medicines Agency (EMA) in 2018. In Korea, the Ministry of Food and Drug Safety granted approval on May 13, establishing Yescarta as the third CAR-T therapy available in Korea, following Novartis' Kymriah (tisagenlecleucel) and Janssen's Carvykti (ciltacaptagene autoleucel). The Korean approval encompasses the following indications: 1) adult 바카라사이트 추천 with DLBCL who relapse or are refractory to first-line chemoimmunotherapy; 2) adult 바카라사이트 추천 with relapsed or refractory DLBCL after at least two prior lines of systemic therapy; and 3) adult 바카라사이트 추천 with primary mediastinal B-cell lymphoma (PMBCL).

At present, Kymriah remains the only CAR-T treatment used in Korea for the treatment of patients with DLBCL. It has attracted attention as a ‘one-shot treatment,’ offering the potential for durable responses with a single dose in relapsed or refractory blood cancers where therapeutic options are limited. Nonetheless, its clinical application is constrained by its positioning as a third-line treatment.

The most notable distinction of Yescarta lies in its status as the first CAR-T therapy in Korea approved for both second- and third-line treatment of DLBCL. According to Kim, this approval introduced the possibility of ‘early CAR-T application’ for patients experiencing poor prognoses at first relapse, thereby enhancing the potential for long-term survival. Given the clinical course of DLBCL, successive relapses are associated with increasing disease aggressiveness. In particular, patients who relapse within one year of first-line treatment are prone to developing treatment resistance, which contributes to markedly poor prognostic outcomes.

◇40% of DLBCL patients experience relapse…Yescarta emerges as a treatment option for ‘high-risk’ cases

DLBCL is the most common subtype of non-Hodgkin's lymphoma (NHL), a hematologic malignancy arising within the lymphatic system. Representing approximately 40% of all NHL cases, it constitutes the most common form of the disease. As incidence increases with advancing age, the number of affected patients in Korea is projected to rise substantially in parallel with the nation’s rapidly aging population.

The current standard of care for 바카라사이트 추천 with DLBCL consists of a complex, multi-step regiment, typically initiated with chemoimmunotherapy, followed by high-dose chemotherapy and hematopoietic stem cell transplantation. However, approximately 40% of newly diagnosed DLBCL 바카라사이트 추천 experience treatment failure, most commonly in the form of relapse after first-line therapy, thereby underscoring the need for effective second-line treatment options.

"The cure rate following first-line treatment for patients with DLBCL varies depending on the report but is generally estimated at approximately 60%. This figure reflects the majority of patients who achieve complete cure with first-line treatment, as well as a small number of patients who ultimately achieve complete cure after experiencing multiple relapses and receiving salvage chemotherapy," Kim explained. "In cases where relapse occurs within one year of first-line therapy, the cure rate declines sharply to 20-30%, underscoring the markedly poor prognosis for this patient population.

"Because cancer tends to become more aggressive with each recurrence, the likelihood of achieving a cure inevitably decreases with repeated relapses. The introduction of Kymriah represented a meaningful advance, as it allowed 35-40% of these difficult-to-treat patients to achieve survival," Kim stated. "Its limitation lies in being restricted to use in the third-line setting or later. The approval of Yescarta is important because it now provides an option for patients who relapse within one year of first-line treatment."

The therapeutic efficacy of Yescarta in the second-line setting was demonstrated in the pivotal ZUMA-7 trial, which formed the basis for its regulatory approval. This phase 3 clinical trial evaluated Yescarta as a second-line treatment in patients with newly diagnosed DLBCL who relapsed within one year of first-line treatment or were refractory and eligible for autologous hematopoietic stem cell transplantation (HSCT). Its efficacy was directly compared with the existing standard approach of ‘salvage chemotherapy followed by autologous HSCT.’

The ZUMA-7 large-scale trial enrolled a total of 359 바카라사이트 추천, with event-free survival (EFS) as the primary endpoint. After a median follow-up of four years, the Yescarta cohort demonstrated a median EFS of 10.8 months, more than fourfold longer than the 2.3 months observed in the standard treatment group (HR 0.42; 95% CI: 0.33-0.55, P<0.0001). Moreover, the proportion of 바카라사이트 추천 who remained free from disease recurrence or progression at two years was markedly higher in the Yescarta group (46%) compared with the standard treatment group (27%). Kim emphasized that these findings are particularly encouraging in the context of the poor prognosis associated with DLBCL 바카라사이트 추천 who relapse or become refractory within one year of first-line therapy.

"The significance of this study lies in the fact that it successfully achieved its primary efficacy endpoint, with the Yescarta group also demonstrating a markedly higher treatment response rate compared with the standard treatment group," Kim further remarked. "At two years, overall survival (OS) reached 60% in the Yescarta group and 51% in the standard group, a difference of roughly 10 percentage points (%p), supporting the potential of Yescarta to extend survival in a clinically meaningful way."

◇Yescarta employs the 'CD28' domain…"Rapid and potent response"

Another key distinction between Yescarta and Kymriah is found in the composition of the chimeric antigen receptor’s (CAR) intracellular costimulatory domain. Kymriah employs the '4-1BB' domain, whereas Yescarta incorporates the 'CD28' domain, leading to differences in both the kinetics and mechanisms of T-cell activation. Although both treatments target the CD19 antigen, the costimulatory domain determines variations in the speed and duration of T-cell activation.

"The costimulatory domain plays a central role in T-cell activation, serving as the critical trigger for initiating the immune response," Kim explained. "Each domain has distinct strengths and weaknesses: CD28 induces a rapid and robust activation, almost like a sprinter, but with limited duration, whereas 4-1BB promotes a slower yet more durable activation profile, like a middle-distance runner."

"From an antitumor perspective, CAR-T therapies incorporating the CD28 costimulatory domain demonstrate greater potency compared to those utilizing 4-1BB. For this reason, Yescarta may represent a valuable option for patients with highly aggressive forms of DLBCL who require more intensive treatment," he further commented. "This enhanced efficacy is accompanied by a relatively higher risk of adverse events, such as cytokine release syndrome (CRS), warranting particular caution in elderly or immunocompromised patients."

◇A new option for recurrent PMBCL patients with limited choices…Overcoming treatment limitations from inadequate treatment plans

Yescarta has also been approved as a third-line treatment for primary mediastinal B-cell lymphoma (PMBCL), a malignancy with limited treatment options, thereby providing an important treatment opportunity for affected patients. "PMBCL is a subtype of DLBCL that is histologically similar but represents a distinct variant. Although its incidence is relatively low, it is characterized by a unique clinical profile, most notably its predominance among younger female patients," Kim explained.

"As with DLBCL, the salvage rate following first-line treatment in PMBCL is approximately 60%, and the prognosis for patients who fail initial treatment remain poor. Considering the limited treatment options available for relapse, the fact that the Yescarta clinical trial introduced a new treatment option is highly meaningful, despite the relatively small number of PMBCL patients enrolled," he emphasized.

Kim argued that while the introduction of new CAR-T therapies has provided renewed hope for Korean 바카라사이트 추천 with limited prospects of achieving a complete cure, institutional improvements remain essential in areas such as coverage and reimbursement to enable broader prescription of these therapies.

"The advent of CAR-T therapies has provided new hope of a complete cure for patients who, in the past, were faced with the grim reality of being told that ‘cure was highly unlikely,'" he said. "Kymriah has already brought about a profound shift in the treatment paradigm for DLBCL, and the approval of Yescarta is expected to further accelerate this transformation."

"Despite these advances, there remains a substantial unmet need among patients who are unable to achieve a complete cure. This underscores the necessity of continuing to introduce additional CAR-T therapies and alternative treatment modalities. At the very least, we must work to decrease the number of patients whose lives are prematurely shortened by cancer," Kim further added.

Kim emphasized that any anticancer drug must ultimately be accessible to 바카라사이트 추천, with affordability as a prerequisite. In other words, insurance coverage is paramount. Kim further explained that although Kymriah is an expensive therapy, its use has increased significantly since it became reimbursed as a third-line treatment.

"A major issue is that current medical fees are not aligned with the realities of CAR-T therapy. This treatment demands substantial manpower and resources, yet such requirements are not adequately reflected in reimbursement rates," Kim remarked. "Because CAR-T therapy is still unfamiliar, it necessitates considerable consultation time. However, in the absence of reimbursement for these efforts, the more treatments a medical institution provides, the greater the financial losses it incurs."

Kim also pointed out the challenges posed by ambiguous insurance standards governing CAR-T therapy. "CAR-T therapy is associated with high costs, and when reimbursement cuts are imposed, medical professionals are unfairly stigmatized as if they were at fault," he stated. "If physicians are held accountable solely through administrative measures, without considering the realities of patient care, who would be willing to continue offering such treatment?"

According to Kim, physicians treating blood cancers at university hospitals undertake CAR-T therapy out of commitment to curing their 바카라사이트 추천. He added that they also derive a sense of accomplishment and pride from being able to deliver such treatment to blood cancer 바카라사이트 추천.

"This is why physicians continue to adopt CAR-T therapy, despite the considerable risks of treatment-related adverse effects. Yet, if current conditions persist, the introduction of even more advanced treatments will face significant barriers to widespread adoption," he urged. "I hope to see systemic changes that more accurately reflect the realities of clinical practice."

On the other hand, 바카라사이트 추천 is expected to be introduced in Korea during the first half of 2026. Gilead Sciences Korea has already initiated the process for insurance coverage following product approval.