Study of the bispecific antibody talquetamab in combination therapies for patients with relapsed or treatment-resistant multiple myeloma following prior treatment with an anti-CD38 antibody and lenalidomide

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 definitively determined. Despite advances in treatment, the therapeutic approach is usually not aimed at a cure (curative) but rather at controlling symptoms and preventing the disease from progressing (palliative). The choice of treatment depends on various factors, such as the patient’s overall health, age, and disease activity. If multiple myeloma returns despite treatment (recurrence) or does not respond well (refractory), a new combination of different medications is usually used, often again involving antibodies, chemotherapy drugs, or new active ingredients. Treatment is tailored individually to the patient’s previous therapy and current condition. The goal remains to keep multiple myeloma under control for as long as possible and to maintain quality of life. Currently, there are limited treatment options available for patients who have already been treated with lenalidomide and an anti-CD38 antibody. Common treatment approaches in this situation include, for example, combinations such as EPd (elotuzumab, pomalidomide, and dexamethasone) or PVd (pomalidomide, bortezomib, and dexamethasone). Although these therapies are well-established, they often show limited efficacy and do not always lead to long-term disease control. New therapeutic approaches include so-called bispecific antibodies such as talquetamab and teclistamab, which link specific immune cells (T cells) to cancer cells so that the cancer cells can be specifically targeted and destroyed. Both talquetamab and teclistamab are already approved for use as monotherapies in patients with relapsed or refractory multiple myeloma, but not yet as combination therapies.

The goal of the MonumenTAL-6 study is therefore to investigate new combination therapies and compare them with the current standard of care in order to improve treatment outcomes for this patient group. For this reason, patients are randomly assigned to three groups. In the two experimental study groups, patients will receive either talquetamab + pomalidomide (Tal-P) or talquetamab + teclistamab (Tal-Tec). In some cases, both groups may receive pre-treatment with dexamethasone prior to the study therapy. In the third group (control group), patients receive the current standard of care—either EPd or PVd—depending on the medical staff’s choice. Assignment is open-label, meaning that both the medical staff and the patient know which treatment they are receiving. Treatment as part of the study will continue until the disease progresses. Follow-up as part of the study will last for up to 6 years and 5 months. The primary endpoint of the study is progression-free survival, i.e., the time during which the disease does not progress.

Women and men with relapsed or refractory multiple myeloma who have already received at least one and no more than four prior lines of therapy are eligible to participate in the study. Patients must have already received treatment including lenalidomide and an anti-CD38 antibody (such as daratumumab). However, patients must not have been pretreated with pomalidomide, teclistamab, or talquetamab.