CAR-T cell therapy as a first-line treatment for mantle cell lymphoma

Mantle cell lymphoma (MCL) is a malignant disease of the lymphocytes, a subtype of white blood cells that are part of the immune system; it affects what are known as B lymphocytes. MCL is classified as a type of non-Hodgkin lymphoma and is most commonly characterized by enlarged lymph nodes, an enlarged spleen, and an elevated number of lymphocytes in the blood. In addition to the lymph nodes, the cancer cells can also occur in the bone marrow and, for example, in the intestines. The causes of MCL are not yet fully understood, but genetic changes and environmental factors play a role. Treatment becomes necessary when patients develop symptoms or when the MCL is clearly progressing. Treatment is then tailored to the patient’s age and physical condition. Typically, treatment consists of a combination of immunotherapy and chemotherapy; however, drugs that specifically target MCL cells have also been used for some time, something that is only possible to a limited extent with conventional immunochemotherapy.  A novel approach that has been shown to be highly effective in many studies is treatment with CAR-T cells: In this procedure, immune cells (T cells) are extracted from the patient and genetically modified so that they can recognize and eliminate the tumor cells once the modified cells are returned to the patient as a single infusion. For MCL, this form of therapy has so far only been approved for advanced-stage disease. This means that other treatments must have already been administered.

The goal of this Phase 2 study is to further investigate the efficacy and safety of CAR-T cell therapy (KTE-X19) as a first-line treatment for MCL in a selected group of patients. Patients will be randomly assigned to two groups as part of the study. Group 1 will first receive two cycles each of ibrutinib + rituximab and ibrutinib + R-CHOP, followed by CAR-T cell therapy and maintenance therapy with ibrutinib for 6 months. In Group 2 (control group), patients will receive standard immunochemotherapy depending on their age (younger or older than 65 years). Regardless of age, patients will then receive 2 years of maintenance therapy with ibrutinib and, if necessary, rituximab. The study is open-label, meaning that both medical staff and patients know which medications are being administered. Treatments as part of the study will be administered for approximately 3 years (control group), during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. Follow-up lasts up to 7 years.

Patients between the ages of 18 and 75 with untreated mantle cell lymphoma are eligible to participate in this study. The disease must be stage 2–4. At least one of the following high-risk features must be present: either a high or intermediate risk according to the MIPI-c risk score—in combination with a high cell proliferation rate (Ki-67 value of at least 30%), a TP53 gene mutation, or overexpression of the TP53 protein in more than 50% of the lymphoma cells. These characteristics indicate a particularly aggressive course of the disease.