05/31/2022
1.1K
Integrated Internal Medical
Seoul
In April 2022, the Korean government has allowed Kymriah, the world’s first approved CAR-T cell therapy known as a “dream anti-cancer treatment,” to be covered by the National Health Insurance of Korea. As a result, patients suffering from diffuse large B-cell lymphoma and leukemia patients under 25 years of age can expect long-term survival without a heavy economic burden. The cost of administering the treatment dropped from 300 million won (approx. 236,000 dollars) to approximately five to ten million won (3,940 to 7,880 dollars). Also, foreign patients who have resided in Korea for more than six months can benefit from the national health insurance. Other foreigners can also get the same treatment at their own expense.
On April 5th, Seoul National University Hospital announced its successful treatment of an 18-year-old leukemia patient using self-produced CAR-T cell therapy, a first in Korea. With this treatment, Korea took the first step to becoming a leader in next-generation CAR-T cell treatment.
Kymriah has grabbed global attention as an innovative treatment because it uses the patient’s own immune cells rather than chemical substances like existing anti-cancer medicines. The treatment is customized as it genetically modifies the patient’s T-cells to attack cancer cells. The merit is that Kymriah results in fewer side effects than cytotoxic drugs previously used. At the same time, the cure rate with Kymriah is higher than other treatments. The development of Kymriah raised hopes of a cure. Still, a hurdle remains: the cost is more than 300 million won (approx. 236,000 dollars) because it is an advanced biological product customized for each patient. However, Kymriah will be more widely used in the Korean medical sector as it will be covered by the national health insurance scheme.
T-Cell Therapy That Selectively Attacks Cancer Cells
Medical workers worldwide have continued research for decades on treating cancers using patients’ own immune cells. Such attempts mostly led to failure in the past because immune cells frequently bypassed cancer cells without attacking them.
Professor Carl June of the University of Pennsylvania, who developed Kymriah, developed a gene modification technology to help patients’ immune cells identify cancer cells. In 2011, his research team extracted T-cells from three terminal patients with chronic lymphocytic leukemia. The team modified the genes to enable them to target cancer cells and then administered them to the patients. The result was astonishing. Cancer cells in two out of three patients completely disappeared. Novartis, a Swiss pharmaceutical company, developed Kymriah based on the professor’s research and made notable achievements in treating diffuse large B cell lymphoma and leukemia.
Which Medical Facilities in Korea Use Kymriah?
According to the Act on Safety and Support for Advanced Regenerative Medicine and Advanced Biological Products, only CAR-T centers approved by the government for handling human cells, etc. can provide Kymriah treatments. Until now, the government designated four hospitals -- Seoul National University Hospital, Severance Hospital, Samsung Medical Center, and Seoul St. Mary’s Hospital, Catholic University of Korea -- as CAR-T centers. More hospitals across the country will be added to the list.
Since patients’ immune cells are used as an ingredient for Kymriah, they are under strict management, just like other ingredients used in anti-cancer drugs. Young-il Koh, Assistant Professor of Hemato Oncology at Seoul National University Hospital said, “Seoul National University Hospital overhauled its facilities in 2021 to comply with the strict requirements from the Ministry of Food and Drug Safety and from Novartis.” As a result, the hospital is fully equipped with the facilities, manpower, and equipment needed for Kymriah treatments. In addition, systems are in place to protect patients from possible side effects after administering the drug.
Merits of Kymriah
① Higher Cure Rate
Kymriah’s cure rate is higher than other treatments. According to a clinical trial of 75 children with acute lymphocytic leukemia, 81% of them were in complete remission after three months of infusion. 73% reached event free survival (EFS) after six months of infusion, and the overall survival (OS) rate was 90%.
② Fewer Side Effects
Anti-cancer treatments usually accompany side effects such as hair loss and a decrease in the number of white blood cells. However, Kymriah has fewer side effects because it is made from the patient’s own immune cells. Moreover, the treatment causes no immunity-related side effects like host reactions, which is observed after stem cell transplantations.
Side Effects Using Kymriah
Kymriah is a genetically modified T-cell. When it meets cancer cells and becomes excessively activated, side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) can develop. These side effects were not found in existing anti-cancer drugs.
Kymriah Treatment Process
Diseases that Can Be Treated with Kymriah
In Korea, Kymriah can be applied to patients under 25 and who have acute lymphocytic leukemia; or to adult patients with diffuse large B-cell lymphoma.
Cases of Kymriah Treatments
※ The above are cases reported by the Seoul National University Hospital (http://www.snuh.org).
CAR-T Centers (as of May 2022)
Seoul National University Hospital, Severance Hospital, Samsung Medical Center, and Seoul St. Mary’s Hospital, Catholic University of Korea.
Seoul National University Hospital became the first Korean hospital to apply internally produced CAR-T cell treatment to an 18-year-old patient with leukemia and succeeded in the treatment. Professor Hyoung-jin Kang of the Pediatric Hematology-Oncology Department and his team led the entire process of producing CAR-T cells and saved the patient through the treatment. This achievement was made in four years after the initial development in 2018. The hospital established an internal CAR-T cell production system by introducing an automated manufacturing platform by Miltenyi Biotec. Manufacturing Kymriah usually takes four to eight weeks, but the Seoul National University Hospital can successfully manufacture CAR-T cells in just 12 days, enabling patients to get treatments quickly. Foreigners can also participate in clinical research on CAR-T cells, but they must pay their own medical expenses, excluding the cost of the CAR-T treatment.
Seoul National University Hospital will immediately apply Kymriah to refractory or relapsed leukemia, which is covered by the national health insurance; and they will continue clinical research on patients with leukemia not covered by the insurance, such as those with minimal residual disease (MRD) and leukemia relapses in the brain and spinal cord. Professor Kang said, “It is meaningful because the hospital created an integrated system covering self-production and infusion of CAR-T cells and the treatment and management of patients.” The hospital plans to upgrade the CAR-T cell development system into a one-stop process by leveraging its own pre-clinical trial system, GMP facilities, and clinical trial facilities. This will further vitalize the development of new CAR-T cells and the initial stages of clinical research in Korea.
Case of CAR-T cell-based treatment at Seoul National University Hospital
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Report by : Reporter Jung-yoon Kim
Review by : Young-il Koh, Assistant Professor of Hemato Oncology at Seoul National University Hospital