New CAR-T cell therapy for previously treated diffuse large B-cell lymphoma (DLBCL) or multiple myeloma

Diffuse large B-cell lymphoma (DLBCL) is a form of non-Hodgkin lymphoma that affects B lymphocytes—a subgroup of white blood cells that play an important role in the immune system. DLBCL is often characterized by rapid enlargement of the lymph nodes, frequently accompanied by involvement of other organs outside the lymph nodes. Typical symptoms include fever, night sweats, and unintentional weight loss. Multiple myeloma (MM) is a malignant disease of the plasma cells in the bone marrow—these, too, belong to the group of B lymphocytes. Since the myeloma spreads in the bone marrow, those affected often complain of bone pain. The exact causes of both diseases have not yet been fully elucidated. However, it is believed that genetic mutations and environmental factors play a role. While a cure can often be achieved in DLBCL through intensive immunochemotherapy, this is only very rarely possible in MM. Myeloma, however, can generally be treated effectively, allowing the disease to remain inactive for a long time. Nevertheless, both DLBCL and MM can recur over time or develop resistance to previous therapies. Most recently, a new form of therapy—treatment with CAR-T cells—has been tested for both diseases. Several CAR-T-cell therapies have since been approved for this purpose. CAR-T cells are cells of the body’s own immune system (T lymphocytes) that are first harvested from the patient and then modified so that they can specifically recognize and attack cancer cells.

The goal of the CARLOTTA01 study is to investigate the efficacy and safety of a newly developed, as-yet-unapproved CAR-T cell therapy. The drug in question is designated MDC-CAR-BCMA001. The CAR-T cells studied in the CARLOTTA01 trial specifically target BCMA, a protein found on the surface of cancer cells that is recognized by the modified CAR-T cells. These are administered as a single intravenous infusion; the dosages vary depending on the dose group. A total of four different dosages are being tested. Each patient receives the CAR-T cells once. All study participants receive this therapy; that is, there is only one study arm and no control group. Both the patients and the treating physicians are aware that the treatment is being administered (open-label). This is a so-called Phase 1 study, the goal of which is to determine the dose that is both optimally effective and well-tolerated—with particular attention to side effects and response to therapy. To this end, patients will be monitored for up to 24 months after treatment to assess the therapy’s efficacy and the occurrence of side effects caused by the medication. The key factor is whether or when the disease progresses again during therapy.

Eligible participants include women and men aged 18 and older with treatment-resistant or relapsed multiple myeloma (MM) or diffuse large B-cell lymphoma (DLBCL). Patients must have already received at least two lines of therapy (MM) or, in the case of DLBCL, no further standard therapy must be available. Prerequisites include stable general health and adequate organ function. Patients with central nervous system involvement or those currently participating in other studies are excluded. Ongoing immunosuppressive therapy also results in exclusion.