"Although CAR-T cell therapy or bispecific antibody respectively offers an advantage for treating follicular lymphoma, CAR-T data demonstrating positive results over 10 years in 60% of patients indicate that it is an effective treatment option."

As various treatment options are introduced to treat relapsed/refractory follicular lymphoma (FL) with a poor prognosis, how these treatments can be utilized is of great interest.

In South Korea, Kymriah (tisagenlecleucel), which is known as the chief CAR-T therapy, was approved for expanded indications in 2023 to treat patients with relapsed/refractory FL who had previously undergone two or more treatments. After that, doctors are gaining treatment experiences with the drug.

During a meeting with Daily Pharm, Dr. Stephen J. Schuster, Professor of the Department of Hematology/Oncology at the University of Pennsylvania Abramson Cancer Center, who has years of prescription experience in the United States, emphasized the necessity of CAR-T therapy for treating follicular lymphoma.

Follicular lymphoma (hereafter, FL) is a type of non-Hodgkin Lymphoma (NHL) that occurs when cells in the lymph system turn malignant. Because the symptoms of the disease progress slowly, about 80% of the cases are identified at stage III or Stage IV after the disease progresses. The prognosis for patients who relapse is poor. 

Dr. Schuster said, "The prevalence of FL seems to be increasing in Asia." He added, "As FL progresses in various ways, clinical characteristics significantly vary by patient."

Dr. Schuster explains that considering the characteristics of FL, characterized by low-risk disease cases and slow disease progression, most diseases can be managed through proactive treatments. The disease becomes problematic if a disease has a poor prognosis requiring more than one treatment due to relapses.

According to Dr. Schuster, data from patients with FL who need more than one treatment indicate that the remission period shortens as patients repeatedly receive treatment.

"About 20% of the patients with FL relapse after two years following the initial treatment. Even after further treatment, the remission period shortens, and patients have a poor prognosis, thereby needing strong treatments, including CAR-T cell therapy," Dr. Schuster said. "Despite increased overall survival, patients repeatedly need treatments, and the disease can become fatal, ultimately leading to death."

There are several treatment options for FL, but Dr. Schuster highlights the clinical benefits of CAR-T cell therapy because CAR-T cell therapy does not require further treatment after the initial therapy.

The clinical effect of Kymriah (tisagenlecleucel) has been proven through the ELARA clinical study regarding relapsed/refractory FL. The four-year long-term follow-up results of the study were presented at the American Society of Hematology (ASH) conference held in December 2024.

The four-year long-term assessment results of the ELARA study (median follow-up period at 53 months) showed that patients with relapsed/refractory FL treated with Kymriah had consistent treatment response over 4 years and a favorable safety profile.

The median progression-free survival (PFS) of all patients was 53.3 months. At 48 months, 50% PFS was reported in all patients, and 66% of patients were reported to have gained complete remission (CR).

"The follow-up on patients who participated in the 2014 study has been about 10 years, and the data indicate that the overall response rate (ORR) is about 80%, similar to the recently presented ELARA clinical study result," Dr. Schuster said. "In contrast to FL requiring repeated blood tests, various scans, and drug administration for additional therapy, CAR-T cell therapy can lessen the physical and mental burden."


Will the introduction of bispecific antibody change the treatment paradigm?..."CAR-T cell therapy's advantage"

Kymriah received expanded indication in April 2023 in South Korea to treat FL, broadening treatment options.

(모네투주맙)However, there are even more options available at clinical practices. For instance, the bispecific antibody Lunsumio (mosunetuzumab) has been introduced.

Regarding this, Dr. Schuster acknowledges the role of bispecific antibodies but favors CAR-T cell therapy, which demonstrates positive long-term results over 10 years.

"Each CAR-T cell therapy and bispecific antibody has an advantage, and there are no concrete answers to the treatment sequence. The CAR-T data demonstrating positive results over 10 years in 60% of patients is unbeatable," Dr. Schuster said.

In particular, Dr. Schuster highlights that antigen can be easily lost during the treatment course of bispecific treatments, like MabThera or mosunetuzumab, that target CD20.

"The biopsy results from patients treated with bispecific antibody drugs showed that 5.5-6% of patients had losses of CD20. However, CD19-targeting CAR-T cell therapy rarely led to losses of CD19," Dr. Schuster remarked.

Dr. Schuster views that bispecific antibody drugs are important but may not replace CAR-T cell therapy. Long-term follow-up data on the remission period and response rate are needed for bispecific antibody treatment outcomes.

Dr. Schuster mentions that drug tolerance is an advantage for Kymriah.

The most common adverse event (AE) of CAR-T cell therapy is cytokine release syndrome (CRS). Kymriah has a relatively low AE rate and low severity.

Dr. Schuster also emphasized, "In the past, there have been cases where FL patients received therapies repeatedly, but ultimately, the disease led to death. However, Kymriah offers a single treatment that can help maintain a remission state. It is also a cost-effective treatment option compared to previous therapies."

Lastly, Dr. Schuster said, "Even if FL patients experience relapse after treatments, they may receive CAR-T cell therapy and maintain remission state for about 10 years, as well as having improved quality of life." He added, "Because an index for predicting survival varies by disease and disease shows characteristics, making a treatment choice through clinical follow-up assessment is important."