Cevostamab in combination with pomalidomide and dexamethasone compared with standard therapy in patients with previously treated multiple myeloma

Multiple myeloma is a type of non-Hodgkin lymphoma and is a malignant disease of plasma cells, which originate from B lymphocytes, a type of white blood cell. Normally, these cells produce antibodies that help the body fight off infections. When plasma cells multiply and become malignant, they develop into myeloma cells that proliferate uncontrollably in the bone marrow. These myeloma cells produce non-functional antibodies (M-proteins), disrupt normal blood cell production, and lead to bone loss. As a result, the disease can cause various symptoms, including bone pain, bone fractures, anemia, and impaired kidney function. Patients with multiple myeloma are also more susceptible to infections. Multiple myeloma occurs predominantly in older adults; most patients are between 70 and 80 years old at the time of diagnosis. If the disease returns after an initially successful treatment (recurrence), several successive courses of treatment are often necessary. Standard therapy for previously treated multiple myeloma includes, among other things, antibodies targeting the surface markers CD38 and SLAMF7 on cancer cells. These include the active ingredients daratumumab, which targets CD38, and elotuzumab, which binds to the SLAMF7 protein on the surface of plasma cells. So-called proteasome inhibitors, such as carfilzomib, are also used. These drugs inhibit the proteasome, a protein complex that breaks down proteins no longer needed by the body’s cells. When this breakdown is inhibited, the unwanted proteins accumulate in the cell and lead to cell death, which is intended to disrupt the growth of cancer cells. Dexamethasone is a corticosteroid—that is, a cortisone-like active ingredient—that is typically administered in combination with other medications for multiple myeloma and directly attacks the malignant myeloma cells. This study is investigating novel active ingredients such as cevostamab, a so-called bispecific antibody that can bind to two different sites simultaneously. It binds to the FcRH5 protein on the surface of myeloma cells and to the body’s own T cells—that is, immune system cells—so that the T cells are brought into close proximity to the cancer cells and can attack them. Pomalidomide belongs to a class of immunomodulatory drugs (IMiDs) that are designed to inhibit the growth of myeloma cells while simultaneously stimulating the body’s own immune response against the cancer cells.

The goal of this Phase 3 study is to investigate whether treatment with cevostamab in combination with pomalidomide and dexamethasone is effective and well-tolerated compared with standard therapy in patients with previously treated multiple myeloma. Patients will be randomly assigned to one of two parallel treatment groups. In the study arm, cevostamab is administered as an intravenous infusion together with pomalidomide as a tablet; dexamethasone is administered as a tablet or as an infusion, in each case prior to cevostamab. In the control arm, patients receive standard therapy selected by the study physicians from approved combinations, which include daratumumab, elotuzumab, or carfilzomib (each in combination with pomalidomide and dexamethasone). The study is open-label (unblinded), meaning that both the patients and the study physicians know which treatment is being administered. The follow-up period is approximately 5 years.

Eligible participants are patients aged 18 and older with confirmed multiple myeloma who have already received one to three prior lines of therapy, including treatment with an anti-CD38 therapy or with lenalidomide.