A Severance Hospital research team said it has confirmed that using mono-immunotherapy for refractory anaplastic lymphoma kinase (ALK)-positive lung cancer has no efficacy.
The finding raises a need for a new direction in the development of immunotherapy for treating ALK-positive lung cancer.
According to the Health Insurance Review and Assessment Service, more than 100,000 patients were diagnosed with lung cancer the last year. Of the total, 80 to 85 percent suffer from non-small cell lung cancer, and ALK-positive lung cancer patients account for about 5 percent of all non-small cell lung cancers, according to the hospital.
In ALK-positive lung cancer, drug-resistant mutations frequently occur, and the central nervous system's metastasis is high, it pointed out.
As the resistance develops within one to two years after the use of targeted therapies and usable drugs after the targeted therapy are also limited, there has been a high unmet medical need for new treatment options.
To test the efficacy of immunotherapy in ALK-positive lung cancer, the team, led by Professors Cho Byoung-chul, Lim Sun-min, Pyo Kyoung-ho, and Park Chae-won, divided an ALK transgenic mouse model into three groups. Afterward, the team administered ALK inhibitors and immunotherapy as either a monotherapy, combination therapy, or sequentially, to confirm the drug's efficacy, side effects, and immune mechanisms.
The researchers discovered that mono-immunotherapy had insufficient tumor suppression effects for treating ALK-positive lung cancer. They also confirmed that while ALK inhibitor monotherapy and combination therapy were effective, the combination therapy showed severe liver toxicity in patients.
When the team confirmed the changes in immune cells and cytokines for each treatment group, the change in T lymphocytes, a major drug action mechanism that attacks tumor cells and kills cancer, was insignificant when using mono-immunotherapy. Also, all of the CD8+ T cells, which play an essential role in tumor suppression, did not show a significant change in the mono-immunotherapy group, while the immunosuppressive cells that suppress the immune function increased.
"This study provides an important basis for the lack of using immunotherapy as a monotherapy in treating ALK-positive lung cancer," Professor Lim said. "As a method to solve this problem, it is possible to suggest the possibility of treatment through further research, such as a combination of a cell therapy agent and various immunomodulatory drugs already developed, or an immunotherapy combination treatment option."
Journal for Immunotherapy of Cancer published the results of the study in its latest issue.