New Maintenance Therapy for Multiple Myeloma Following Stem Cell Transplantation: Comparison of Iberdomid Alone or in Combination with an Antibody (Isatuximab)

Multiple myeloma is a cancer of the bone marrow in which certain immune cells, known as plasma cells, multiply uncontrollably. Plasma cells produce antibodies, which are important for fighting off infections in healthy individuals. The causes of the disease have not been fully elucidated. Despite advances in treatment, the therapeutic approach is usually not aimed at a cure (curative), but rather at controlling symptoms and preventing the progression of the disease (palliative). The choice of treatment depends on various factors, such as the patient’s overall health, age, and disease activity. It often involves a combination of chemotherapy drugs followed by high-dose chemotherapy with the reinfusion of the patient’s own stem cells, which were collected beforehand (autologous stem cell transplantation, ASCT). If this initial treatment is successful—that is, if the disease responds to therapy—patients typically receive maintenance therapy. This is intended to delay the recurrence of the disease for as long as possible. Currently, the immunomodulator lenalidomide is most commonly used for this purpose. The study drug Iberdomid belongs to a new generation of immunomodulators known as CELMods (Cereblon-E3-ligase modulators). It works similarly to lenalidomide by destroying abnormal plasma cells while simultaneously activating the immune system. However, its effect is stronger and remains effective even against cells that have already developed resistance to lenalidomide. Iberdomid is already approved for relapsed or refractory multiple myeloma—that is, when the disease has been shown to progress again despite treatment or when the disease cannot be controlled. However, the drug is not yet approved for first-line maintenance therapy, as used in this study. The second study drug, isatuximab, is a so-called CD38 antibody. It specifically targets the surface protein CD38, which is particularly common on myeloma cells. As a result, isatuximab helps the immune system recognize and specifically destroy these cancer cells. Isatuximab is already approved for the treatment of advanced multiple myeloma; however, this study is the first to investigate its use as part of maintenance therapy following a stem cell transplant. Dexamethasone is also used as part of the maintenance therapy. This is a corticosteroid that, among other things, can enhance the effectiveness of the other medications and reduce unwanted side effects (such as inflammation). The goal of this Phase 3 study is to investigate the efficacy and safety of the drug Iberdomid, both alone and in combination with isatuximab, as maintenance therapy for multiple myeloma, and to compare the two treatments. To this end, patients will be randomly assigned to two groups. One group will receive Iberdomid for a period of 36 months. Patients in the other group will receive Isatuximab in addition to Iberdomid, also for 36 months. Iberdomid is taken as a tablet; isatuximab is injected under the skin (subcutaneously). In both groups, patients receive dexamethasone as a tablet or infusion during the first treatment cycle. The study is open-label, which means that both healthcare professionals and patients know which medications are being administered. Treatment success is measured by whether myeloma cells are still detectable in the bone marrow (known as minimal residual disease, MRD). As with standard treatment, MRD is monitored regularly throughout the entire treatment period. The study places particular emphasis on determining how many patients no longer have detectable myeloma cells after 24 months (MRD negativity). Overall, patient data will be collected over a period of up to 60 months. Eligible participants include women and men aged 18 and older who have been diagnosed with newly diagnosed multiple myeloma and who participated in the previous GMMG-HD8/DSMM XIX study. As part of the previous study, patients must have received high-dose chemotherapy with autologous stem cell transplantation. In addition, the disease must have responded to the initial treatment, achieving at least a partial remission (partial regression of the disease). Pregnancy must be ruled out, and reliable contraception is required throughout the entire treatment period.