D., recently presented a case of advanced chronic lymphocytic leukemia (CLL) with a rather poor prognosis in the United States, who achieved complete remission (i.e., normalization of all test parameters) after a single personalized cell therapy, also known as chimeric antigen receptor-modified T-cell (CAR-T) therapy, without conventional chemotherapy, and whose remission has lasted for more than four years. This case illustrates that immunotherapy will be a new avenue of treatment for chronic lymphocytic leukemia, in addition to the use of targeted drug therapy. The patient is currently under long-term follow-up observation to determine whether immunotherapy can completely eradicate the leukemia cells in the patient’s body.
Currently, allogeneic hematopoietic stem cell transplantation is the only way to cure CLL, but its clinical use is significantly limited due to the high number of complications and relatively high mortality rate, the professor said. In addition, targeted drugs for CLL, such as ibrutinib (manufactured by Pharmacyclics/Janssen in the U.S. under the trade name Imbruvica), are very effective, but the chances of patients achieving complete remission are not high. As a result, CLL remains “a disease that cannot be cured with conventional approaches and requires the development of newer, better-targeted and more effective therapeutic agents. According to Paul Barr of the University of Rochester Wilmot Cancer Center in New York, it is important that new therapies are developed so that different treatments can be used for different disease conditions, with some patients benefiting from CAR-T therapy and others from ibrutinib or edelaris therapy, ultimately leading to individualized treatment. CAR-T cells were first used for the treatment of tumors by Dr. Porter in the United States. CAR-T cells have a therapeutic effect on CLL, acute lymphoblastic leukemia and non-Hodgkin’s lymphoma and have been found to have a long-lasting effect. In his CTL019 trial protocol, started in 2010, there are still 14 cases of advanced relapsed/refractory CLL in long-term complete remission, with some cases in not only long but deep remission. Of these cases, 29% (4 cases) achieved complete remission with cell therapy, with CR up to 53 months in the first case, 52 months in the second case, 28 months in the third case, and 21 months in the fourth case, before dying from postoperative infection of basal cell carcinoma of the lower extremity skin. In addition, 10 patients had neither progression nor death within 10 months. the most important feature of CAR-T cell immunotherapy for CLL was that patients could achieve durable remission, and in addition to 4 CR cases, 4 others achieved partial remission with a median time to remission of 7 months.
All patients were very sick and had undergone repeated multiple chemotherapy treatments before receiving experimental immunotherapy, and a few had received bone marrow transplants. Therefore, the investigators tried to find the most suitable patients for immune cell therapy among the high-risk, treatment-naïve patients. Of note were the side effects, eight patients treated with CAR-T cells developed a mild to severe cytokine release syndrome (CRS). Its symptoms included fever, myalgia and nausea; in severe cases, hypotension, edema and hypoxia. Strategic treatment for CRS included the application of an interleukin-6 antibody (Tocilizumab), and after treatment, four patients with CRS recovered completely. Cytokine release syndrome and other adverse effects, such as neurological symptoms and B-cell deficiency, are side effects specific to CAR-T cell therapy, and multicenter studies have been initiated to explore how best to manage these side effects. Dr. Porter also found that cytokine release syndrome is related to the level and duration of CAR-T cell expansion in the body. the longer CAR-T cells are in the body, the longer they look for tumor cells and the more effective they are in fighting tumors.
According to the professor, scientific research has shown that through long-term in-depth studies of patients in complete remission, modified T cells can stay in the patient’s body for many years after intravenous input, continuing to exert anti-tumor effects and causing the disappearance of tumorigenic B cells. It is hoped that the patient’s remission period will continue to be prolonged, eventually leading to a cure.