CAR-T treats Hodgkin's lymphoma
The purpose of the clinical study conducted at the Multidisciplinary Lineberg Cancer Center at the University of North Carolina and Baylor College of Medicine in Houston was to evaluate the safety and effectiveness of immunotherapy in patients with Hodgkin's lymphoma. The researchers demonstrated that the treatment was safe; in addition, it showed unexpected efficacy in patients with recurrent or persistent forms of Hodgkin's lymphoma who reacted poorly to other powerful treatments. The therapy led to the complete disappearance of the tumor in most patients treated at the highest dose, and almost all patients showed clinical improvement.
For CAR-T immunotherapy, T-lymphocytes are taken from patients and genetically modified to recognize proteins present in cancer cells. After being injected into the blood, they circulate for several months, attacking the patient's cancer cells. In some cases, patients are injected with CAR-T cells created from donor T-lymphocytes.
CAR-T therapy has had remarkable success in some clinical trials in the last decade, and has already been approved by the FDA for the treatment of acute lymphoblastic leukemia and diffuse B-large cell lymphoma. In these diseases, CAR-T cells target the CD19 protein, which is found in malignant cells.
In the USA, Hodgkin's lymphoma affects more than 200,000 people. About 85% of patients recover or achieve long-term stable remission after standard chemotherapy and radiation therapy. The remaining patients either do not respond to standard therapy, or they have frequent relapses. Many of these treatment-resistant and relapsing patients are forced to receive powerful treatment for years without any improvement.
In a pilot study involving seven patients with refractory or recurrent Hodgkin's lymphoma, published in 2017, it was found that CAR-T therapy targeting the CD30 protein associated with Hodgkin cells is safe, but gives a fairly modest result.
In the new study, which included 41 patients, the group used the same anti-CD30 CAR-T strategy, but added a mode of lymphodepletion (elimination of own cells capable of reducing the activity of CAR-T lymphocytes with chemotherapeutic drugs) before the introduction of modified CAR-T cells.
This creates a more favorable environment for CAR-T lymphocytes to multiply and damage target cells.
Side effects of lymphodepletion and subsequent CAR-T therapy included flu-like symptoms due to a cytokine storm – a massive release of cytokines, but mostly the severity was weak. None of the patients experienced serious, life-threatening complications, such as brain edema, which was described in CAR-T studies against other types of hematological diseases.
The study showed that anti-CD30 CAR-T therapy was very active against refractory and recurrent Hodgkin's lymphoma.
Fludarabine was chosen for lymphodepletion, because the results of its use were the best. The researchers found that out of 32 patients with active Hodgkin's lymphoma who received fludarabine to create lymphodeficiency before starting CAR-T therapy. A complete response to treatment was observed in 19 patients (59%). Of these, 61% had no signs of relapse within a year. In general, 94% of the treated patients were alive a year after treatment.
Thus, the new tactic showed significant antitumor activity without pronounced toxicity. This means that this treatment will not require hospitalization of patients. The results are very encouraging, but they need to be confirmed in a larger study.
The authors plan to conduct further studies of CAR-T therapy separately and in combination with other new immunomodulatory antitumor drugs.
Article by C.A.Ramos et al. Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma is published in the Journal of Clinical Oncology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UNC Lineberger Comprehensive Cancer Center: Excellent research results for CAR-T therapy against Hodgkin lymphoma.