CAR-T cell therapy with Liso-cel as first-line treatment for people with central nervous system lymphoma who are not eligible for autologous stem cell transplantation

Primary central nervous system lymphoma (PCNSL) is a rare cancer of the lymphatic system. It occurs only in the brain, spinal cord, or cerebrospinal fluid. The central nervous system is surrounded by a protective barrier called the blood-brain barrier. Therefore, treatment requires the use of special medications that can cross the blood-brain barrier. The drug methotrexate, in particular, has proven to be effective. The standard treatment involves intensive chemotherapy, followed by high-dose chemotherapy and the reinfusion of the patient’s own stem cells (autologous stem cell transplant), which were previously collected from the blood and frozen. However, this treatment is not suitable for all patients, particularly older adults or those with certain comorbidities. The HCT-CI score is used to assess the risk of mortality due to comorbidities in the context of a stem cell transplant. If the score is > 3, the therapy is not suitable. Alternative treatment options are being investigated for this group of patients. Liso-cel (lisocabtagene maraleucel, trade name Breyanzi) is a CAR-T cell therapy. In this therapy, the body’s own immune cells (T cells) are collected from the blood and modified in the laboratory so that they can recognize and attack cancer cells. The modified cells are returned to the body, where they specifically target and attack the cancer cells.

The goal of this Phase 2 study is to investigate the efficacy and safety of the CAR-T cell therapy Liso-cel as a first-line treatment. All patients will receive the same treatment, which consists of several steps. First, T-cells are collected from the blood and modified in the laboratory into CAR-T cells (Liso-cel). Since this process can take several weeks, patients will undergo bridging chemotherapy in the meantime. Patients receive a combination of the antibody rituximab and chemotherapy consisting of high-dose methotrexate with procarbazine or temozolomide. Before receiving Liso-cel, patients also undergo preparatory treatment with the chemotherapy drugs fludarabine and cyclophosphamide. This is followed by a single infusion of Liso-cel. The study is open-label (not blinded). This means that both patients and medical staff know which treatment is being administered. The primary objective of the study is to assess progression-free survival 12 months after the Liso-cel infusion. This refers to the period during which the disease does not progress. Additional objectives include the complete and overall response rates, duration of response, event-free survival, overall survival, and quality of life.

Patients aged 18 years or older with histologically confirmed PCNSL are eligible to participate. Patients must be ineligible for an autologous stem cell transplant, meaning they must be at least 65 years old or have an HCT-CI score of at least 3. In addition, patients must be eligible for high-dose methotrexate treatment. Patients are excluded if they have previously received CAR-T cell therapy or other gene therapy, have an HIV infection, active hepatitis B or C, or an active autoimmune disease requiring immunosuppression.